To investigate a possible interaction between norfloxacin and theophylline, eight healthy nonsmoking volunteers (mean age 27 .+-. 5.3 years) were admininistered aminophylline, 5 mg/kg, before and after a 6-day course of norfloxacin, 400 mg every 12 hours, and changes in pharmacokinetic parameters were measured and compared. Norfloxacin induced significant decreases in theophylline clearance (14.9%; p < 0.01) and the terminal phase slope (13.3%; p < 0.02) and increased the AUC (16.6%; p < 0.01). The apparent volume of distribution at steady state was unchanged. The greatest norfloxacin-induced individual change in theophylline clearance was a reduction of 28.6%. Given these findings, we advise that, for patients who are treated with theophylline and are subsequently treated with norfloxacin, adjustment of the theophylline dosage may be necessary in some patients to minimize the risk of theophylline toxicity.