No comparative epidemiological data can be found in the literature on the renal safety of acidsuppressing drugs. We followed-up a cohort of close to 180,000 persons during periods of treatment and non-treatment with ®ve anti-ulcer drugs to evaluate the risk of idiopathic acute renal failure and/or nephrotic syndrome. After reviewing medical records, ®ve patients were found to be cases. Two presented with acute renal failure and three had nephrotic syndrome. Three cases occurred during periods of non-exposure to anti-ulcer drugs. Two cases occurred during current use of ranitidine: one of acute renal failure and one of nephrotic syndrome. No case was encountered during treatment with cimetidine, famotidine, nizatidine or omeprazole. The incidence of idiopathic renal disease in the general population was 1 per 100,000 person-years. The relative risk associated with use of acidsuppressing drugs was 1.8 (95% CI, 0.3±10.7) compared to non-use. These results do not suggest a major increased risk for acute renal injury and/or nephrotic syndrome associated with use of anti-ulcer drugs.