31 patients with coronary artery disease (11 patients with diabetes mellitus and autonomic neuropathy. 10 patients with diabetes without neuropathy, and 10 patients with asymptomatic myocardial ischemia) participated in a study designed to investigate whether there is a difference in forearm skeletal muscle ischemia and pain threshold. The degree of ischemia was determined by plethysmographically measured reactive hyperemia. There was no difference in maximum reactive hyperemia after passive forearm ischemia of 5-min duration in the three groups. After symptom-limited ischemic work, there was significantly more reactive hyperemia in patients with silent myocardial ischemia as compared to diabetic patients. Exercise time was longer in patients with silent myocardial ischemia (153 +/- 51 s) than in patients with diabetic neuropathy (139 +/- 45 s) and diabetics without neuropathy (120 +/- 45 s). Pain as a cause of termination of symptom-limited ischemic forearm exercise occurred less frequently in patients with diabetic neuropathy (2/11) and patients with silent myocardial ischemia (3/10) as compared to patients with diabetes without neuropathy. Patients with silent myocardial ischemia had a higher ischemic tolerance in the ischemic working forearm than did diabetic patients with and without neuropathy. In patients with neuropathy, however, ischemic pain occurred less frequently at the same ischemic work level compared to diabetics without neuropathy. Therefore, diabetic neuropathy appears to facilitate the occurrence of silent myocardial ischemia. The data presented here suggest that there is a qualitative difference in ischemic tolerance between patients with silent myocardial ischemia and patients with diabetic neuropathy.