ABSTRACT Smallpox vaccination in the United States is a routine public health measure which has been under intensive review during the last decade. The most frequently occurring adverse reactions to vaccination are benign and require little or no systemic therapy. These reactions include accidental infection, erythematous and urticarial rash, and generalized vaccinia. Chickenpox occurring concurrently with vaccination presents no problem unless vaccinia has widely superinfected the chickenpox lesions. There is no risk to the pregnant woman who is vaccinated, but there is a slight risk that the fetus will develop fetal vaccinia. The vaccinia does not cause congenital malformations. Vaccinia hyperimmune globulin (VIG) in prophylactic dosage may be given to a pregnant woman who is traveling to a smallpox infected or endemic area in order to prevent fetal vaccinia. Vaccinia necrosum and eczema vaccinatum require vigorous systemic therapy with VIG, and often thiosemicarbazone. Post-vaccinial encephalitis, while frequently serious, has not been shown to be ameliorated by VIG therapy, although there are data which suggest VIG has some value in prophylaxis for encephalitis. Prophylaxis, prompt recognition, and proper therapy may reduce the fatality rates of these complications. Revaccination of patients who have suffered a complication is a frequent clinical problem. Revaccination of an individual who has had post-vaccinial encephalitis or vaccinia necrosum is contraindicated unless the risk of contracting smallpox outweighs the risk of the above two diseases. Revaccination of children who have had eczema vaccinatum is not contraindicated. Revaccination of children with a history of accidental infection or erythematous or urticarial rash presents no known or theoretically increased risk.