INCLUSION CRITERIA:

• Age: 18-32 (Volunteers over 32 years of age are not included since they usually are not vaccinia-naive.) Children are excluded due to concerns of safety, including autoinoculation.
• Acceptable medical history by screening evaluation form and brief assessment.
• Negative urine pregnancy test for women.
• Negative history of smallpox vaccination.
• Negative ELISA for HIV or negative Western blot for volunteers who have a positive ELISA and have participated in an HIV vaccine trial.
• Availability for follow-up for planned duration of the study (6 months). Note: Stage 1 - clinic visit at Day 180+/-15 days, Stage 2 - phone call at Day 180 +/- 15 days.
• If the volunteer is female, she agrees to use acceptable contraception and not become pregnant for the duration of the study.
• Willing to sign informed consent.
• Adequate renal functions as defined as a serum creatinine of 1.5 mg/dL, urine protein < 100 mg/dL or negative proteinuria, and a calculated creatinine clearance > 55 mL/min based on the following formulas: For males ((140 minus age in years) x weight in kg)/72 x serum creatinine). For females: 0.85 x ((140 minus age in years) x weight in kg)/72 x serum creatinine). Note: Renal function is measured to ensure subjects could meet criteria for use of cidofovir if needed.

EXCLUSION CRITERIA:

• History of immunodeficiency.
• Serology positive for HIV, hepatitis B, or hepatitis C at the screening visit.
• Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease.
• Diabetes mellitus.
• Moderate to severe kidney impairment.
• Malignancy, other than squamous cell or basal cell skin cancer.
• Autoimmune disease.
• Use of immunosuppressive medication.
• Corticosteroid nasal sprays are permissible.
• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol.
• History of "illegal" injection drug use.
• Live attenuated vaccines within 60 days of study.
• Use of experimental agents within 30 days prior to study.
• Any history of vaccination with any vaccinia vectored or other pox vectored experimental vaccine.
• Typical vaccinia scar without known history of vaccination.
• History of smallpox vaccination.
• Acute febrile illness on the day of vaccination.
• Pregnant or lactating women.
• Eczema or any degree or history of eczema.
• History of exfoliative skin disorders/conditions.
• Any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm.
• Receipt of blood products or immunoglobulin in the past 6 months.
• Household contacts/sexual contacts with, or occupational exposure to (other than minimal contact), people with any of the following: pregnancy, < 12 months of age, eczema or history of eczema, previously listed skin disorders/conditions, immunodeficiency disease or use of immunosuppressive medications.
• Allergies to any component of the vaccines (e.g. polymyxin B sulfate, dihydrostreptomycin sulfate, chlortetracycline hydrochloride, neomycin sulfate).
• Allergies to any known component of the diluent.
• Allergies to any known component of VIG, i.e., thimerosal or previous allergic reaction to immunoglobulins.
• Allergies to cidofovir or probenicid.
• Blood donation within the past 55 days (stage 1 only).