Alcohol ingestion commonly accompanies cocaine abuse, but the effects of chronic cocaine-alcohol abuse on the circulation are undefined. Therefore, to test for evidence of cocaine-alcohol cardiac dysfunction and interference with cardiovascular nervous system reflexes, 10 normal volunteers (group I), 8 asymptomatic alcoholic patients (group II), and 15 age matched, asymptomatic cocaine and alcohol abusers (group III) underwent screening two-dimensional echocardiography, electrocardiography, a series of autonomic nervous system tests, and upright bicycle exercises. Echocardiographic indices did not differ among groups. R wave voltage was increased in group III, probably primarily due to a smaller body surface area. Heart rate (HR) and/or systolic blood pressure (SBP) responses to 60 degree tilt and to hyperventilation differed in group III (decreased HR response, while SBP increased inappropriately). Despite excellent exercise tolerance, HR response to exercise in group III (compared to group I) was decreased. These results suggest impairment of certain autonomic nervous system reflexes and, possibly, sinus node dysfunction from cocaine-alcohol abuse.