There is increasing evidence that cocaine can have serious adverse effects on the heart. Angina, myocardial infarction, coronary artery spasm, arrhythmia, and sudden death have been reported in association with its use. There have been only two reports of actual myocardial pathology. In an attempt to clarify the pathophysiology of cocaine-associated cardiotoxicity and to search for pathologic changes that might be useful forensically, we reviewed random microscopic sections of hearts from 30 cases of cocaine-associated death seen by the San Francisco Medical Examiner. The age of the patients at death ranged from 25 to 74 years (mean 33.9 years). Pathologic findings included the presence of mild atherosclerotic coronary artery disease without evidence of thrombosis in three cases, associated with mild interstitial fibrosis in one case as well as mild focal myocardial fibrosis without coronary disease in four other cases. The most notable abnormality was the presence of myocardial contraction bands in 28 (93 per cent) cases. In comparison to 20 control cases of death secondary to sedative-hypnotic overdose, the hearts from the cases of cocaine-associated contained significantly more myocardial contraction bands (P less than .001; two-sided). The diffuseness of the contraction bands correlated directly with the level of cocaine found in the urine and blood at autopsy during routine screening. The presence and number of contraction bands in these cases was independent of other drugs found in the urine and blood, the number of sections of myocardium examined, and a history of attempted resuscitation. Contraction bands may act to supply the anatomic substrate for the arrhythmias associated with cocaine use. They may also provide a morphologic marker that can be sought in suspected cases of lethal cocaine overdose. Their presence may also suggest a cause of death in cases of sudden and unexpected death in which autopsy reveals no other pathology, and a drug screen is positive for cocaine.