During a clinical trial of orally administered ciprofloxacin in respiratory tract infections, changes in serum theophylline levels were evaluated in 33 hospitalized patients who also required theophylline therapy. Patients received intravenous theophylline in standard titrated doses and 750 mg of oral ciprofloxacin twice daily. Serum theophylline levels in all patients were measured before and during ciprofloxacin therapy. The mean serum pretreatment theophylline level was 7.8 +/- 4.6 micrograms/ml; during ciprofloxacin therapy, the level increased to 14.6 +/- 7.4 micrograms/ml. Twenty of the 33 (61 percent) patients evaluated had increases in serum theophylline levels by a mean value of 10.5 micrograms/ml. In 30 percent of patients who experienced increases, theophylline concentrations were in the toxic range. This occurred more frequently in elderly patients with chronic obstructive pulmonary disease. In light of the frequency and potential severity of this interaction, careful monitoring of serum theophylline levels in patients receiving theophylline and ciprofloxacin is recommended.