Inclusion Criteria:

Eligible participants for this study:

• Are between the ages 18-65 years of age
• Are daily cigarette smokers
• Have smoked a minimum of 10 cigarettes per day for at least one year
• Are confirmed smokers as verified by CO
• Have a psychiatric diagnosis of schizophrenia or schizoaffective disorder (any subtype) as determined by the SCID-IV. Participants must have received a stable dose of antipsychotic medication for at least 2 weeks prior to beginning the study. Patients receiving clozapine at 500 mg/day or more must also be receiving anti-seizure prophylaxis. Patients must be determined to be psychiatrically stable at baseline as established by standardized interview and medical review by psychiatrist.

Exclusion Criteria:

Individuals who are not eligible to participate in this study include individuals with:

• Any serious or unstable medical problem in the last 6 months
• Severe renal impairment
• A history of clinically significant allergic reactions to nicotine agonist medications
• Current primary use of tobacco products other than cigarettes
• Breath alcohol level > 0.005 g/l at screening
• Current substance abuse or dependence (besides nicotine)
• Current attempts to quit smoking using any method
• Designation as legally incompetent to sign the informed consent (i.e., have a guardian or have delegated power of attorney to another).

Other exclusions are:

• Current use of medications that might affect the behavioral response to cigarette smoking, including transdermal nicotine or nicotine gum and bupropion - Inability to participate in the screening session due to severe psychosis, severe depression or suicidality, current mania, or an organic mental disorder such as dementia or delirium
• Presence of unstable psychiatric symptoms or clinical deterioration (i.e., unstable psychosis, homicidality, or suicidality) within the last month.
• Females of childbearing potential are eligible if not pregnant or nursing and if they practice effective contraception (oral, injectable, or implantable contraceptives; intrauterine device; or barrier method with spermicide).
• There currently are no known contraindications to the use of varenicline and no identified drug-drug interactions. However, reduced dosage of varenicline is recommended for individuals with severe renal impairment.