In a prospective multicentre trial, the influence of schedule, compliance, age, sex and weight on the antibody response to hepatitis B vaccination was investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n = 143) and 0, 1, 2, 12 months (group 2; n = 141) was performed in months 3, 7 and 12. In addition, the antibody response was compared one month after the third and one and six months after the last vaccination. Seroprotection rates (anti-HBs greater than 10 IU/l) and antibody titres, given as geometric means (GMTs), were higher in group 1 at month 12 as well as one month after completion of three immunizations. More vaccinees of group 2, however, showed seroprotection at month 3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and six months after the last vaccine dose. Determination of parallel corrected correlation factors demonstrated that age was the most important single factor, followed by body weight and sex. However, no more than 3% of the variation in the GMT can be explained by the influence of age. Due to decreased compliance with the four-dose schedule with a drop-out rate of approximately 10% of the vaccinees, the total percentage of initial vaccinees who in the end developed protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12 months schedule as more rapid protection is obtained and the higher antibody levels after the booster vaccination at month 12 provide longer protection. However, vaccinees whose compliance might be questionable over a period of 12 months, should be selected for the vaccination 0, 1, 6 months schedule as compliance is at a higher level over this period and advantage can be taken of the booster effect of the third dose given in month 6.