To evaluate the effect of maintenance oral theophylline therapy on the diagnostic efficacy of dipyridamole-thallium-201 single photon emission computed tomography (SPECT) imaging for coronary artery disease, dipyridamole-thallium-201 SPECT imaging was performed in eight men with documented coronary artery disease before initiation of theophylline treatment and repeated while these patients were receiving therapeutic doses of oral theophylline. Before theophylline treatment, intravenous dipyridamole caused a significant increase in heart rate, decrease in blood pressure, angina in seven of eight patients, and ST segment depression in four of eight patients. While they were being treated with theophylline, none of the patients had angina or ST segment depression, and there were no hemodynamic changes with intravenous dipyridamole. Before theophylline treatment, dipyridamole-thallium-201 SPECT imaging showed reversible perfusion defects in myocardial segments supplied by stenotic coronary arteries. With theophylline treatment, dipyridamole-thallium-201 SPECT showed total absence of reversible perfusion defects. Treatment with theophylline markedly reduced the diagnostic accuracy of dipyridamole-thallium-201 imaging for coronary artery disease.