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Bolus application of endotoxin to healthy volunteers results in reversible hemodynamic alterations, such as observed in septic cardiomyopathy. Currently, endotoxin-induced cardiodepression is mainly attributed to the endotoxin-induced release of proinflammatory cytokines into the circulation, particularly of tumor necrosis factorαand interleukin-1, the serum levels of these cytokines being enhanced in sepsis and septic shock, and also in various heart diseases. In this study, we report a proinflammatory effect of endotoxin (1–10μg/ml, 24-h incubation period) on neonatal rat cardiomyocytes in serum-free culture, evidenced by induction of inducible nitric oxide synthase, enhanced release of nitrite (protein synthesis-dependent) and interleukin-6 into the supernatant, as well as an increase in cell-associated interleukin-1 and a specific cardiodepressant profile: endotoxin disruptsβ-adrenoceptor-mediated increase in pulsation amplitude, butα-adrenoceptor-induced increase in pulsation amplitude and arrhythmias are not suppressed. In the presence of dexamethasone (0.1μm), the endotoxin-mediated blockade ofβ-adrenergic responsiveness, as well as induction of inducible nitric oxide synthase, enhanced nitrite release and interleukin-1/-6-production are inhibited. In contrast, tumor necrosis factorαat a low concentration (10 U/ml) depressesα- andβ-adrenergic responsiveness in the presence of dexamethasone in a nitric oxide-independent manner. These data suggest a stimulatory effect of endotoxin on the cardiomyocyte and a specific proinflammatory and nitric oxide-dependent cardiodepressant profile of endotoxin.