To investigate the role of the cold pressor test (CPT) with radionuclide angiocardiography in the diagnosis of coronary artery disease (CAD), we performed angiocardiography in 52 patients (18 with angiographically normal coronary arteries and 34 with CAD) during the resting state, CPT, and supine bicycle exercise (EX). In normal subjects, left ventricular ejection fraction (EF) was unchanged between rest (58 +/- 9%) and CPT (59 +/- 9%, p = ns), but increased during maximal EX (69 +/- 9%, p less than 0.01). In CAD patients, EF fell from 55 +/- 9% at rest to 49 +/- 9% during CPT (p less than 0.01), and to 53 +/- 11% during EX (p = ns vs. rest). Twenty-seven CAD patients (79%) developed new or worsening areas of dyssynergy during CPT, vs. 25 patients (73%) during EX. Thus, the cold pressor test with radiocardiography appears to be a useful noninvasive test for the diagnosis and functional evaluation of CAD, particularly in patients unable to perform a satisfactory exercise test.