To determine the incidence of and risk factors for adverse reactions following the boosters, we conducted a nationwide prospective study of persons receiving pre-exposure booster vaccination with human diploid cell rabies vaccine (HDCV). Persons who had previously received three pre-exposure doses of HDCV and whose rabies neutralizing antibody titres were < or = 1:5 were enrolled in the study if they stated that they intended to receive a booster. Of the 98 persons enrolled in the study, 40 (41%) were in risk groups for whom boosters are not recommended. Three (3%) of 98 developed generalized urticaria or wheezing within 1 day of receiving boosters and three others (3%) developed urticaria 6 to 14 days after the booster. No differences were found between individuals with reactions (either type) and those with no adverse reaction according to age, gender, occupation, history of previous allergies, or time since or route of primary vaccination. Reactions were somewhat more common among persons who received primary vaccinations by the intramuscular route (i.m.) and booster vaccinations by the intradermal route (i.d.) (3/15, 20%) or primary vaccinations i.d. and booster vaccinations i.m. (2/10, 20%), and somewhat less common among persons who received both these vaccinations i.d. (1/52, 2%) or i.m. (0/7). The number of persons who develop allergic reactions may be minimized by administering vaccinations only when vaccination is strictly indicated. The influence of the route of primary and booster vaccinations on the development of reactions deserves further study.