The effect of cimetidine on gastrointestinal (GI) symptoms in patients taking non-steroidal anti-inflammatory drugs was studied in a multicentre, double-blind, placebo-controlled 4 week trial. Five hundred and seventy osteoarthritis patients received cimetidine 400 mg bid or placebo. Seventy-nine % in the cimetidine group had no GI symptoms at week 4 compared to 72% in the placebo group (p = 0.07). Only 5.6% in the cimetidine group reported heartburn compared to 19.2% in the placebo group. Diarrhoea was more pronounced in cimetidine treated patients; 18.5% compared to 2.7%. In a subgroup of patients with previous GI discomfort on NSAID therapy (N = 123), 63% reported disappearance of symptoms in the cimetidine group compared to 45% in the placebo group (p = 0.05). In patients with GI symptoms starting NSAID therapy and in patients on NSAID with a heartburn problem, cimetidine seems to be of value.