On the basis of reports that diltiazem may bind to the hepatic microsomal enzymes and inhibits the metabolism of some co-administered drugs, and to determine the effects of diltiazem on theophylline pharmacokinetics in patients with bronchospastic airway disease, we have investigated the effect of a 180-mg daily dose of oral diltiazem during 5 days on theophylline clearance in eight patients with that disease. Theophylline half-life increased 24%, from 5.7 +/- 1 to 7.5 +/- 1.8 h (p < 0.05), and total body theophylline clearance showed a decrease of 22%, from 87.3 +/- 20 to 68.3 +/- 18.6 ml/min (p < 0.05) after diltiazem therapy. The apparent volume of distribution was unchanged. This reduction in theophylline clearance is likely produced by inhibition of its metabolism by diltiazem. A clinically important drug interaction may occur with theophylline when diltiazem therapy is given concurrently in patients with bronchospastic airway disease.