This study will investigate the potential for secondary transmission of vaccinia from smallpox vaccination sites covered by various types of dressings, as well as the effects of each dressing type on the healing of the vaccination lesion. The results could have great implications for infection control and public health in the wake of potential mass smallpox vaccination. The study population will consist of two cohorts: healthy individuals who are naive to the smallpox vaccine ("naive group") and healthy individuals who have had previous vaccination with the smallpox vaccine ("experienced group"). Individuals in each group will be vaccinated with a dose of smallpox vaccine diluted to 1:5 and will be randomized to receive one of three dressing preparations to cover the vaccination site: standard 2 inch x 2 inch gauze attached to the skin via paper tape ("Gauze dressing"); Opsite gauze-impregnated occlusive dressing ("occlusive dressing"); and Allevyn hydropolymer dressing (Smith and Nephew, "hydropolymer dressing"). In addition, 30 of the 108 subjects (15 naïve and 15 experienced) will be enrolled as a "cardiac subgroup" and will have additional blood drawn for the assessment of specific biochemical markers related to thrombosis and platelet activation (specifically, plasminogen-activator inhibitor type 1 (PAI-1) and soluble CD40 ligand (sCD40L). The primary study objective will be the assessment of infectivity of vaccination sites via evaluation of vaccinia growth from specimens of the outer dressing for each bandage type. Positive culture reflects failure of the bandage to prevent possible spread of vaccinia. Secondary study objectives include the following: assessment of infectivity of vaccination sites via evaluation of vaccinia growth from specimens from the hand contralateral to the vaccine site for each dressing type; comparison of the rate of lesion healing (time from vaccination until lesion is deemed "well-healed") for each dressing cohort; association of adverse events (AEs) involved with transmission of vaccinia, such as autoinoculation and secondary dissemination, with the type of dressing covering the vaccination site; and determination of the alterations after smallpox vaccination in the body's endogenous fibrinolytic system to investigate the potential pathophysiology of adverse ischemic cardiac events seen in vaccinated subjects in the recent civilian and military campaigns. The tertiary objectives of the study include: assessment of the overall safety profile in each cohort, as determined by reactogenicity of the vaccine and the development of expected and unexpected AEs unrelated to dressing type; assessment of the efficacy of a 1:5 dilution of APSV in vaccinia-experienced adults as measured by the proportion of individuals who respond to vaccination with a "take: 6-11 days after vaccination; characterization of the humoral immune response generated following vaccination in each cohort; assessment of pharyngeal carriage and shedding of vaccinia virus in each cohort of vaccinated volunteers; and assessment of the tolerability of the dressing and total number of bandage changes determined from a volunteer questionnaire and summarized by bandage type. Volunteers will be followed for 56 days following their primary vaccination. Volunteers who do not have a "take" will be offered revaccination under a separate protocol after their 56-day blood sample is drawn. All volunteers will be contacted by telephone for information about serious adverse events at or about 180 days after their primary vaccination.