Inclusion Criteria:

1.1. Who. Subjects will be women and men between the ages of 18 and 40 who have smoked at least 10 cigarettes per day for at least 1 year. They will respond to requests in the public media for individuals who are interested in quitting smoking.

1.2. Total sample/Number per group. The total randomized sample size will equal 20 subjects, equally distributed across the two medication groups.

1.3. Inclusion Criteria.

1. 18 years to 60 years.
2. Smoke Marlboro Lights (This criterion was selected to reduce inter-subject variation in response variables as has been done in many human laboratory studies of smoking behavior. Over 40% of all smokers smoke some type of the Marlboro brand of cigarette (Substance Abuse and Mental Health Services Administration, 2005). Based on telephone screen data for 767 subjects collected at TURC, Marlboro Light cigarettes are the most common type of Marlboro smoked in our sampling population (158/252 Marlboro users [63%]). Therefore, we have decided to only enroll those smoking Marlboro Light cigarettes, non-menthol).
3. Smoked at least 10 cigarettes/day for at least 1 year.
4. English speaking and reading.

5. Females who are of childbearing potential must practice effective contraception and meet the following criteria:

   1. Are instructed to avoid pregnancy through 30 days after the last dose of study medication.
   2. Have a negative urine pregnancy test at baseline.
   3. Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication.
6. Willingness to not use illicit drugs during study period including marijuana.

Exclusion Criteria:

1. Concurrent use of tobacco products (other than cigarettes) or nicotine products.
2. Medications that might affect the outcome measures of nicotine reward, cognition, anxiety, and stress will also be a basis for exclusion. These medications include psychotropic drugs (i.e., anti-psychotic, anti-depressant, anti-anxiety, or stimulant), anti- hypertensive agents (e.g., beta-blockers), and other drugs that can influence the outcome domains.
3. History of kidney disease or renal impairment since varenicline is primarily excreted by the kidney and thus such patients are vulnerable to increased and potentially toxic levels of varenicline.
4. Treatment for drug or alcohol dependence during the last year, or evidence of alcohol abuse so severe that the patient is judged potentially unable to comply with the protocol.
5. Suicidal or homicidal ideation.
6. History of bipolar disorder, schizophrenia, schizoaffective disorder, attention deficit disorder, or attention deficit hyperactivity disorder.
7. Current major depression or anxiety disorder.
8. Pregnant or lactating or planning pregnancy during treatment period.
9. Having plans to leave the immediate geographical area within 2 months.
10. Unwillingness or inability to give written informed consent.