The present study was initiated to determine whether the myocardial effects of an in vivo injection of endotoxin into rats were correlated with the dose and thus the lethality of the endotoxin administered. All animals in this study were used 4 h after a bolus injection of 1,000, 100, 10, or 1 microgram/100 g body wt of Escherichia coli endotoxin. At this time, mean arterial blood pressure had returned to control levels but cardiac output was still depressed at the three higher doses as previously reported [Am. J. Physiol. 248 (Regulatory Integrative Comp. Physiol. 17): R471-R478, 1985]. Intrinsic function of the myocardium was assessed using the isolated perfused working heart preparation. Cardiac output and pressure development were measured at varying preloads and at two levels of aortic outflow resistance. In vitro approaches were chosen for this study to eliminate peripheral vascular changes and humoral or neural alterations that might influence myocardial performance in vivo. Results indicate that coronary vascular resistance was increased in all hearts from endotoxin-treated animals compared with controls. In addition, myocardial performance was impaired at several doses of endotoxin, and the degree of dysfunction was dependent on the dose of endotoxin administered. Dysfunction, i.e., a depression in cardiac output times peak systolic pressure, was evident at the two higher doses in which there was 50 and 10% lethality by 24 h and also in the lower dose of 10 micrograms/100 g, which was nonlethal. Cardiac output appeared to be very sensitive to the consequences of endotoxin administration. Defects in myocardial performance could be revealed by increasing preload or afterload stress on the hearts.(ABSTRACT TRUNCATED AT 250 WORDS)