The application of cyclic AMP as a marker of myocardial ischemia in humans with coronary artery disease has been investigated during pacing-induced angina. Cyclic AMP was determined by a radioimmunoassay. In 15 patients myocardial lactate extraction at rest (20 +/- 12%) converted to production levels (-30 +/- 23%) during angina (p less than 0.0005). Insignificant changes occurred in coronary venous plasma cyclic-AMP levels. The mean myocardial cyclic-AMP extraction at rest (0.3 +/- 8.7%) converted to small release values (-6.0 +/-11%) during angina (= n.s.). No significant correlation was found between myocardial lactate and cyclic-AMP uptake or release. Therefore, cyclic AMP is an insensitive marker in the evaluation of myocardial ischemia.