Twenty-four patients with moderately controlled insulin dependent diabetes with a duration of diabetes ranging from 2 to 10 years as well as 17 control subjects were vaccinated against hepatitis B virus using Gen Hevac B vaccine. The vaccine was injected 0.5 mL intramuscularly into the deltoid region on three separate occasions at intervals of 1 month. If subjects were still negative for anti-hepatitis B surface antigen (HBs) or had inadequate antibody after the third injection, a fourth administration of vaccine was given 3 months later. The mean anti-HBs titer was 243.3 +/- 97.2 mi.u./mL in control subjects and 39.8 +/- 53.2 in diabetic patients (P < 0.001). In the control group optimal protection was obtained in 100% of subjects, whereas 11 diabetic patients (45.8%) had low anti-HBs titer (< 10 mi.u./mL). All of 11 diabetic patients showed adequate (> 10 mi.u./mL) anti-HBs titer after the fourth dose of vaccine. In diabetic patients the most striking feature was the reduced CD4/CD8 ratio which was significantly lower (P < 0.001) than that of the control group. We conclude that diabetic children have an impaired immune response to hepatitis B vaccine. It is suggested that diabetic children should be vaccinated against hepatitis B virus with four injections instead of three.