Nine healthy subjects received single doses of intravenous aminophylline (5 mg/kg) on four occasions separated by at least 1 wk. One trial was a control; the other three were performed during administration of therapeutic doses (250 mg every 6 hr) of tetracycline, erythromycin, and cephalexin. Theophylline concentrations in multiple plasma samples drawn during 24 hr after each dose were determined by high-pressure liquid chromatography. Mean kinetic variables for theophylline during control, tetracycline, erythromycin, and cephalexin trials, respectively, were: volume of distribution, 0.57, 0.61, 0.63, and 0.62 l/kg; elimination half-life (t1/2), 7.9, 9.2, 10.3, and 8.6 hr; total clearance, 0.90, 0.84, 0.78, and 0.89 ml/min/kg. In no case did differences between treatment conditions approach significance. Thus there is no consistent evidence of a kinetic interaction between theophylline and three commonly prescribed antibiotics.