Interaction between ciprofloxacin and theophylline was studied in eight male volunteers, who were randomly divided into two groups. All subjects were given intravenous theophylline and indocyanine green (ICG) on study days 0, 7 and 14. Group I subjects received ciprofloxacin 750 mg orally every 12 h on days 1-7. Group II subjects received ciprofloxacin 750 mg every 12 h on days 6-14. No significant changes in ICG clearance or half-life were noted. A significant increase in theophylline half-life and volume of distribution was observed (P less than 0.05); however, clearance was not significantly decreased (P = 0.1). A potentially clinically significant interaction was detected in three subjects whose theophylline clearance decreased by 42-113%. Until further clinical experience is gained, we advise caution when these agents are coadministered. Some adjustment in theophylline dosage may be required; therefore, these patients should have serum theophylline concentration measurements and careful clinical assessment for theophylline toxicity.