Thallium-201 myocardial scintigraphy was performed during cold pressor stimulation in 36 patients aged 36 to 69 years. Thirty-one patients had coronary artery disease and 5 patients did not, as confirmed by coronary cineangiography. Thallium-201 (1.5 to 2 mCi) was injected at 30 seconds of the cold pressor stimulation. The product of systolic pressure X heart rate increased from a baseline of 77.4 +/- 16 (standard deviation [SD]) to 103.6 +/- 17 at 30 seconds of the cold pressor test (p less than 0.0005). Transient perfusion deficits developed in 24 of 31 patients with coronary artery disease (sensitivity 77%), and all 5 patients without coronary artery disease had normal scintigrams. The sensitivity in detecting coronary artery disease was 40% in patients with 1 vessel disease, 91% in patients with 2 vessel disease, and 100% in patients with 3 vessel disease. Exercise electrocardiograms (available in 29 of 36 patients) were positive for ischemia in 18 of 24 patients with coronary artery disease and in 1 of 5 patients without coronary artery disease (sensitivity 75% and specificity less than 80%). Exercise thallium-201 scintigrams, obtained in 16 patients, were positive in 11 patients with coronary artery disease and positive cold pressor thallium-201 scintigrams. Five patients without coronary artery disease and with normal cold pressor thallium-201 scintigrams had normal exercise thallium-201 scintigrams. Coronary cineangiography performed during cold pressor stimulation in 6 patients who had positive cold pressor and exercise thallium-201 scintigrams did not show coronary spasm. Our data indicate that cold pressor thallium-201 scintigraphy offers promise as a noninvasive test in the diagnosis of coronary artery disease and may be used in patients in whom exercise testing is not feasible.