The efficacy of hepatitis B (HB) vaccine alone or combined with hepatitis B immunoglobulin (HBIg) in preventing hepatitis B virus (HBV) infection was studied in a controlled trial. Recombinant HB vaccine (Engerix-B, 20 micrograms) was given to 40 susceptible health-care workers within three days of exposure (Group B). In another group of 37 medical professionals a single dose of HBIg (0.06 mg/kg) was administered intramuscularly within three days of exposure, followed immediately by the first dose of vaccine (20 micrograms dose) (Group A). In both groups the next doses of recombinant vaccine were administered one, two and six months later. One month after the fourth dose of vaccine the percentage of incidence of antibody to hepatitis B virus surface antigen (anti-HBs) was 94.6% in group A and 95% in group B with geometric mean titer of antibodies of 340 and 380 mIU/ml, respectively. A control group consisted of 34 persons who did not receive any specific immunoprophylaxis (Group C). All subjects were followed for at least ten months. The protective value of immunization, both active alone and combined passive and active, was clearly effective since none of the recipients developed acute symptomatic HBV infection compared with two (6%) of 34 not immunized persons (Fisher's exact test p = 0.01). Thus, in the absence of evidence of lesser efficacy for the use of HB vaccine alone after exposure to HBsAg-positive blood, this schedule would seem to be the treatment of choice in adult persons.