The purpose of this study was to investigate the effect of norfloxacin on theophylline elimination. Ten normal volunteers were studied. In a randomized crossover sequence, each subject received 6 mg of aminophylline per kg of body weight by a 30-min intravenous infusion on day 4 of taking norfloxacin (400 mg every 12 h) or while drug free. Mean theophylline clearance decreased and mean elimination half-life increased after norfloxacin administration (from 0.036 +/- 0.006 to 0.033 +/- 0.004 liter/h per kg and from 8.7 +/- 1.2 to 9.5 +/- 1.5 h, respectively; P less than 0.05, Wilcoxon signed-ranks test). We conclude that norfloxacin taken in recommended doses for 3 days has a small inhibitory effect on theophylline metabolism that would probably not cause clinically important elevations in theophylline concentrations in most patients.