This study would like to test whether the combination of ondansetron and olanzapine will be superior to placebo at decreasing self-reported heavy drinking among early onset alcoholics.

Target population: We will enroll male and female who meet DSM IV criteria for alcohol dependence and who are currently drinking equal or more than 21 alcohol units/week for women and equal or more than 28 alcohol units/week for men in the 7 day period prior to enrollment.

This is a double-blind placebo-controlled study. Eligible subjects will be randomized to ondansetron (4 ug/kg) and olanzapine (9, 18, 36 ug/kg) vs placebo. All subjects will participate in a 9 week regimen of weekly BBCET and outpatient medication treatment.

Inclusion Criteria:

• Males and females who have given written informed consent
• Aged 18 years and above and weighing ≥40 kg and ≤140 kg
• Drinking on average ≥21 and ≥28 drinks/week for women and men, respectively, in the 7-day period prior to enrollment
• DSM-IV-R diagnosis of alcohol dependence
• Good physical health as determined by a complete physical examination, electrocardiogram (EKG) within normal limits and laboratory screening tests within acceptable range
• Negative pregnancy test at intake.
• Literate in English and able to read, understand, and complete the rating scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments
• Willing to participate in behavioral treatments for alcoholism
• Answer an advertisement in the newspaper/radio/television, and express a wish to stop drinking
• Provide evidence of stable residence in the last month prior to enrollment in the study, and have no plans to move in the next three months

Exclusion Criteria:

• Any current axis I DSM-IV psychiatric disorder other than alcohol or nicotine dependence that warrants treatment or would preclude safe participation in the protocol
• Severe alcohol withdrawal symptoms that, in the physician's opinion, require inpatient treatment
• Serious medical comorbidity requiring medical intervention or close supervision, or any condition that can interfere with the receipt of ondansetron or olanzapine
• Severe or life-threatening adverse reactions to the ondansetron or olanzapine medications in the past or during this clinical trial
• Female subjects who are pregnant, lactating, or not adhering to an acceptable form of contraception at any time during the study
• Received inpatient or outpatient treatment for alcohol dependence within the last 30 days
• Significant medical illness (including hypertension) as determined by history and/or complete physical examination.
• Gross neurological disease
• Mental retardation
• Pyrexia of unknown origin
• Diagnosis or suspicion of Alzheimer's disease
• Clinically significant abnormalities on the EKG that will preclude safe participation
• Recent (last 3 months) history of ischemic heart disease or myocardial infarction.
• Current infective hepatitis as evidenced by clinical manifestations. If hepatitis is suspected, a hepatitis antibody/antigen screen will be done.
• Participation in a clinical study within the last 30 days
• Elevation of liver enzymes
• History of any severe or life-threatening reaction to olanzapine or ondansetron
• Past or current history of seizures disorder
• Past or current history of diabetes
• Being treated with any medication with potential for clinically significant interactions with alcohol or olanzapine and/or ondansetron. These include:, serotonin antagonists (e.g., ritanserin or buspirone), dopamine antagonists (e.g., haloperidol), or compounds with actions similar to disulfiram (Antabuse®).
• Pending imprisonment