1 Renal function was studied in nine patients with chronic peptic ulcer before and at repeated intervals during treatment with cimetidine (1.6g daily). 2 Plasma creatinine concentration was significantly increased on the first day after starting cimetidine, and at 3 weeks, but not at 12 weeks. Blood urea concentration was unchanged. 3. Clearances of creatinine 51Cr EDTA and 125I-hippuran were significantly reduced within 6 h of starting cimetidine. Clearances of 51Cr EDTA and 125I-hippuran returned to baseline within 3 weeks, and creatinine clearance within 12 weeks. 4 Urinary creatine excretion was significantly increased at 3 weeks, but there was no significant change in urinary creatinine excretion, or in serum creatine phosphokinase concentration. 5. These observations suggest that cimetidine causes an early but short-lived fall in glomerular filtration rate (GFR) and effective renal plasma flow. The later rise in plasma creatinine was unaccompanied by any change in GFR, and may have been due to competition by cimetidine for renal tubular handling. 6 Caution should be exercised when administering cimetidine to patients with pre-existing renal failure.