A defect in the immune response of patients with chronic renal failure leads to low response rates and insufficient antibody concentrations following a number of highly recommended vaccinations. This has been shown before for immunization against hepatitis B and influenza. Few data are available concerning the efficacy of vaccination with tetanus toxoid in these patients. In a prospective, controlled study we vaccinated seronegative patients with chronic renal failure not on dialysis, patients on chronic intermittent hemodialysis, and patients after kidney transplantation with tetanus toxoid. The results were compared with those of a control group consisting of 13 age-matched patients with mild essential hypertension and normal kidney function. Only 11 of 20 (55%) patients in the chronic renal failure group and 16 of 23 (69%) in the dialysis group had a protective antibody response after triple vaccination. In contrast, all the patients in the control group and six of seven transplant patients seroconverted. The response to tetanus toxoid was highly associated with the response to a previously administered vaccination against hepatitis B. Responders to this vaccination also had a better response rate to tetanus toxoid. The antibody concentrations after vaccination were lower in all patient groups compared with the controls; the lowest titers were found in the transplant patients. Therefore, renal patients will need revaccination much earlier, and tetanus toxoid antibody levels should be checked if a patient is injured and potentially requires vaccination.