Hepatitis B is a serious epidemiological problem in uremic patients treated with renal replacement therapy. A high proportion of hemodialyzed patients do not respond to the standard method of intramuscular (i.m.) hepatitis B vaccination. Low-dose intradermal (i.d.) inoculations and supplementary i.m. injections have been reported to improve the responsiveness in formerly non responding uremic patients. We applied a inoculation schedule of 10 microg Engerix B i.d. in 49 pts and i.m. (control group) in 13 pts once a week during 12 consecutive weeks in order to compare the effectiveness of the various ways of immunization in maintenance dialyzed patients not responding to standard vaccination. Serum anti-HBs antibody level, as well as biochemical and immunological parameters were examined. Already one month after initiation of the cycle, 57.1% of patients in the i.d. group responded by achieving the minimum protective anti-HBs antibody level (>10 IU/I.); while 14.3% reached full adequate anti-HBs antibody level (>100 IU/I.). After the full therapy period, anti-HBs antibody level >100 IU/I. was achieved in 42.9% of the patients, while a total of 81.7% of patients reached the anti-HBs antibody level >10 IU/I. In 18.4% of patients no response was observed. Surprisingly similar results were achieved in the i.m. group. Twelve months after termination of the inoculation cycle we noted decrease of anti-HBs antibody level; the values >100 IU/ I. was observed only in 18.4% of the study group, while 87.8% reached a titre >10 IU/I. We found a relationship between the effectiveness of immunization and RBC count, total serum protein and albumin levels and GGTP activity. Mitogen stimulation indexes in both groups were 4-5 times lower in comparison to reference values in the general population. In the study group that did not respond to vaccination, mitogen stimulation indexes were 2 times lower as compared to the group characterized as having a good response. In conclusion, the route of injection seems to be less important than the frequency and number of doses of the vaccine. Anemia and malnutrition may be responsible for the worse response to vaccination against hepatitis B virus.