We have previously reported that cocaine treatment of mice with viral myocarditis significantly increases neutrophil infiltration into the myocardium and exacerbates the inflammatory response. The mechanism of these effects is unknown, but we have proposed that cocaine may increase circulating catecholamines and consequently increase inflammatory cell adhesion to the coronary endothelium. Here we examined the hypothesis that cocaine enhances inflammatory cell infiltration via catecholamine-induced up-regulation of cell adhesion molecule (CAM) expression in adult BALB/C mouse hearts. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (E-selectin) and leukocyte adhesion molecule-1 (L-selectin), were detected by gene array analysis, reverse transcriptase-polymerase chain reaction RT-PCR, Western blotting and immunohistochemical staining. CAMs were significantly up-regulated in cocaine-pretreated mouse hearts. Beta-adrenergic stimulation with epinephrine also up-regulated CAM expression, confirming the effects obtained with cocaine. Beta-adrenergic blockade with propranolol inhibited epinephrine-induced CAM expression. In hearts perfused with polymorphonuclear neutrophils (PMN), an increased adhesion of PMN to the coronary endothelium was observed in cocaine-treated and epinephrine-treated mouse hearts compared to control hearts. Blocking antibodies against ICAM-1, E-selectin and L-selectin significantly inhibited epinephrine-enhanced PMN adhesion, while anti-VCAM-1 had lesser effects. Our findings suggest that cocaine-induced neutrophil infiltration is mediated by beta-adrenergic stimulation through up-regulation of CAM expression, which enhances PMN adhesion. Conversely, beta-adrenergic blockade with propranolol inhibits the effects of cocaine and epinephrine on CAM expression and decreases PMN adhesion to the coronary endothelium. These observations may be of significance for the development of preventative and therapeutic approaches to patients with cocaine or catecholamine-induced myocarditis.