Nine healthy male volunteers were studied to assess the interaction between theophylline and ciprofloxacin and to assess whether a similar interaction occurred with lomefloxacin, using a randomised, crossover design. Subjects received theophylline 125 mg 8 hourly with and without lomefloxacin 400 mg 12 hourly or ciprofloxacin 500 mg 12 hourly for 7 days. Ciprofloxacin treatment lowered total theophylline clearance by 27%, owing to a decreased clearance via 1‐, 3‐demethylation and 8‐ hydroxylation. Lomefloxacin treatment did not alter theophylline clearance. Ciprofloxacin, at usual clinical doses, could cause a clinically significant interaction when co‐administered with theophylline. 1990 The British Pharmacological Society