During a 19-month period we determined the incidence of bacterial infection among 39 patients treated with desferrioxamine who had end-stage renal disease and were undergoing maintenance hemodialysis. Twenty-three received desferrioxamine because of aluminum-related bone disease, and 16 because of iron overload. A control group of 193 patients on maintenance hemodialysis but without desferrioxamine was used. No difference was found in the incidence of septicemia or of all bacterial infections between the patients with aluminum-related bone disease treated with desferrioxamine and the control patients (0.12 vs. 0.12 septicemia per patient-therapy-year, p greater than 0.05; 0.23 vs. 0.26 bacterial infections per patient-therapy-year, p greater than 0.05). The incidence of septicemia in patients treated with desferrioxamine for iron overload, however, was almost three times that in the control patients (0.36 vs. 0.12 septicemia per patient-therapy-year, p less than 0.01). To assess the effect of iron overload itself, we determined the frequency of bacterial infection in patients on regular hemodialysis who have never received desferrioxamine. These were subdivided into three groups according to serum ferritin level which indicated normal or low iron stores (Group I: serum ferritin 10-330 micrograms/l, n = 125), moderate (Group II: serum ferritin 331-1000 micrograms/l, n = 49) or more advanced iron overload (Group III: serum ferritin 1001-2000 micrograms/l, n = 10). Compared to patients with normal or low serum ferritin levels (Group I), we found a significantly higher rate of bacterial infection among patients in Group II compared with Group I (0.18 vs. 0.34 infections per patient-therapy-year, p less than 0.05) and Group III compared with Group I (0.18 vs. 0.58 infections per patient-therapy-year, p less than 0.01). These results suggest that treatment with desferrioxamine does not favour the development of septicemia or bacterial infection independently of iron overload and that iron overload itself may predispose patients on regular hemodialysis to bacterial infection.