A prospective study was performed in 40 chronic uremics which included: (1) the intramuscular administration to all patients of 40 µg of a DNA-recombinant vaccine (Engerix-B) at 0,1,2,6 months; (2) an intramuscular booster dose of 40 µg at 18 months in patients having an anti-HBs titer > 100/ml at the 7th month (group A); (3) a further intramuscular supplementary dose of 40 µg at 12 months (besides that at 18 months) in patients developing an antibody titer 10 mlU/ml) was achieved, and then every month for a total of 6 months in patients who did not develop a protective titer even after 19 months (group C). At the end of the study, all patients had developed a protective titer: 77.5% after the 4th intramuscular dose, 12.5% after the 5th and 10% after 3.5 ± 0.5 (mean ± SEM) intradermal inoculations. The mean antibody titers were 1,461 ± 98 mlU/ml in group A, 594 ± 684 in group B and 131 ± 133 in group C. In conclusion, our two-step integrated protocol gives an anti-HBs protective titer in all our