A 63-year-old man with ventricular tachycardia (VT) refractory to drug therapy was admitted for surgical ablation of the VT with coronary artery bypass graft surgery. He developed increased theophylline concentrations with decreased calculated theophylline clearance after propafenone therapy for recurrent VT was initiated. Within 1 day after the addition of propafenone 150 mg every 8 hours to a drug regimen that included theophylline sustained-release tablets 300 mg every 12 hours, the patient demonstrated increased theophylline serum concentrations and decreased calculated theophylline clearance. Despite a decrease in theophylline dosage, theophylline concentrations continued to rise as the dosage of propafenone was increased to 300 mg every 8 hours. Theophylline was discontinued due to a rising theophylline level, improved oxygenation, and absence of wheezing. Both propafenone and theophylline are hepatically metabolized by the cytochrome P-450 enzyme system. The decrease in theophylline clearance of 25% to 69% in this patient may be due to competitive metabolism resulting in enzyme inhibition and increased theophylline concentrations. Since propafenone and 5-OH-propafenone levels were not measured, it is unknown whether propafenone clearance was affected as well. Health care practitioners should be aware of this possible drug interaction and monitor theophylline concentrations and the electrocardiogram closely if the agents are coadministered.