Inclusion Criteria:

• Healthy adults; age > 18 years, date of birth > 1972
• HIV-1 negative as documented by ELISA and Western blot analysis within 4 weeks immunization
• Normal history and physical exam
• Lower risk sexual behavior as defined by AVEG
• Normal complete blood count and differential defined as:
• hemoglobin > 11.0 gm/dl
• white blood cell count greater than or equal to 2500 cells/mm3
• platelet count between 150,000 and 550,000 cells/mm3
• total lymphocyte count greater than or equal to 650 cells/mm3
• CD4+ T cell count greater than or equal to 400 cells/mm3 Normal AST and ALT (<1.5 x the laboratory upper normal limit) and creatinine < 1.1 X ULN Normal CPK-MB (creatine kinase isoenzyme MB) and troponin I Normal ECG Negative PPD Availability for one year of follow-up No evidence of smallpox vaccination (born in the USA after 1972 with no detectable scar (on the deltoid, ankle, thigh or between the scapulae), and no history of vaccination in personal immunization record) No entry into military service before 1990 Informed consent

Fewer than 3 of the following:

Current cigarette smoker History of high cholesterol History of diabetes or high blood sugar High blood pressure Heart disease before age 50 in parent or sibling Vaccinia virus seronegative

Exclusion Criteria:

• History of immunosuppressive illness, chronic illness, or use immunosuppressive medications (e.g. steroids) or treatments
• Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol. Specifically excluded are persons with a history of suicide attempts, recent suicidal ideation or who have past or present psychosis
• Subjects with identifiable higher risk behavior for HIV infection as determined by screening questions designed to identify risk factors for HIV infection. Specific exclusions include:
• History of injection drug use within the last 12 months prior to enrollment
• Higher or intermediate risk sexual behavior as defined by the AVEG
• Live attenuated vaccines within 60 days of study (subunit or killed vaccines [e.g. influenza or pneumococcal] are not exclusionary, but should be given at least 2 weeks away from HIV immunization)
• Use of experimental agents within 30 days prior to study
• Receipt of blood products or immunoglobulin in the past 6 months
• History of eczema, atopic dermatitis and other acute, chronic or exfoliative conditions
• Pregnant or lactating women
• Household contact with persons with immunodeficiency (including eczema or use of immunosuppressive medications)
• Household contact with persons less than 12 months of age
• Household contact with pregnant women
• Subjects with serious, life-threatening allergies to the antibiotic gentamicin
• Refusal of women to practice birth control for 3 months following vaccination.
• Known cardiac disease such as previous myocardial infarction, angina, congestive heart failure, or cardiomyopathy