Inclusion Criteria

• Meets DSM-IV criteria for hypochondriasis; ascertained by Structured Diagnosis for Hypochondriasis module of SCID-I, and meets a hypochondriasis severity rating of at least "moderate"
• Drug free for 6 weeks of all psychoactive or investigational medications (seven weeks for fluoxetine) (Use of zolpidem or similar non-benzodiazepine hypnotics will be allowed).
• Approval from treating physician if concomitant psychoactive medications need to be withdrawn prior to study participation
• English fluency and literacy

Exclusion Criteria

• Pregnant or nursing mothers and women of childbearing potential who are not taking adequate birth control precautions
• Any of the following Axis I mental disorders: chronic pain syndrome, schizophrenia, schizoaffective disorder, delusional disorder, bipolar disorder, alcohol abuse or dependence disorder (current or within the last six months), or substance abuse or dependence disorder (current or within the last twelve months). Patients with other comorbid psychiatric disorders are eligible based on the following three criteria: hypochondriasis must be the predominant presenting disorder; patient can not have a major co-morbid psychiatric disorder rated as "severe" on the Clinical Global Impressions Scale (CGI Scale); and patients can not have a co-morbid psychiatric disorder that causes significant functional impairment (significant functional impairment will be defined as an impairment that interferes in a marked way with expected role functioning, vocational and/or interpersonal).
• Suicidality within the last 6 months as established by a score of 9 or more on the suicidality module of the MINI Plus.
• Symptom-contingent pending litigation, disability compensation, or workers' compensation proceedings
• Major medical illness expected to worsen significantly, lead to hospitalization, or likely to prove fatal in the next six months, established with the Cumulative Illness Rating Scale (CIRS); Stable, chronic medical illness is not an exclusion criterion
• Not able to withdraw from concomitant psychoactive medications or currently taking necessary other medication that might interact adversely with fluoxetine:

A) Taking psychoactive medications for psychiatric indications (i.e., DSM-IV psychiatric disorders) who prefer not to discontinue these medications or for whom discontinuation would be clinically inadvisable B) Taking medications that may interact adversely with fluoxetine: theophylline, certain anti-arrhythmic, warfarin, codeine, monoamine oxidase inhibitors, coumadin, digitoxin, flecainide, linazeline (Zyvox), or vinblastine C) This will not prevent partcipants taking stable doses for at least three months of medications prescribed for non-psychiatric indications, e.g. antidepressants for chronic pain, sedating antidepressants or anti-anxiety agents for insomnia, anti-convulsants for pain, from participating in the study. Participants will be allowed to remain on propanol during this study but will have their blood pressure and pulse monitored every four weeks. Use of tricyclic drugs concomitantly will result in exclusion from the study, unless the dose of tricyclic drugs is low (i.e. 10 mg for patients on doxepin or amitriptyline for sleep). Ascertained by patient report and the judgment of the study psychiatrist.

• Clinically important abnormalities in ECG, laboratory tests (including thyroid function) or physical examination. "Clinically important" abnormalities are those that signify a treatment intervention is needed or a medical abnormality has not been sufficiently addressed. Patients with medical problems that are stable and chronic are eligible, but patients with medical problems that are unstable, acute, or inadequately evaluated will be excluded. A current electrocardiogram is required for all patients with symptoms suggestive of cardiac disease, including chest pain, dyspnea, palpitations, or lightheadedness; if no current electrocardiogram exists, the study will obtain one.
• History of severe side effects associated with fluoxetine or noncompliance with prior CBT for hypochondriasis
• Previous adequate trial of either fluoxetine (eight weeks of which two weeks were at a minimum dose of 60 mg/day) or CBT for hypochondriasis (at least four sessions specifically targeting hypochondriacal symptoms) will be excluded, regardless of prior response. Inability to ambulate or mobility restrictions that prohibit frequent travel to the hospital for treatment and evaluation.