The relationship between diminished response to hepatitis B vaccine in renal failure patients and serum creatinine level, age and other factors is unknown. The immune response of patients with renal failure of varying severity to hepatitis B vaccine was determined in this study. Sixty-eight patients with renal failure of varying severity who were negative for hepatitis B markers received four doses of hepatitis B vaccine, and anti-HBs titers were determined at 0, 1, 2, 3, 6, 8 and 12 months. Maximum anti-HBs titers were seen at 8 months. At this time 86% of patients with creatinine < or = 4 mg/dl but only 37% with creatinine > 4.0 mg/dl had a protective titer of > or = 10 mIU/ml (p < 0.002). Age was inversely related to anti-HBs titer (p = 0.045) and was independent of serum creatinine in predicting antibody response. We conclude that all patients with chronic renal failure should be immunized against hepatitis B as early as possible in the development of their disease, to ensure maximum response, and to minimize the effects of elevated serum creatinine and increasing age.