Sympathetic nervous system activity and myocardial response to adrenergic stimulation were studied in the rat during endotoxicosis. Plasma glucose concentration, adrenal norepinephrine (NE) and epinephrine (E) content, spleen NE content, and myocardial NE and cAMP content were analyzed in fed rats given saline or endotoxin (ETOX, 16.7 mg/kg). Values were determined at various times during a 6-hour period or at the agonal stage of shock. Myocardial cAMP content was reduced by 1 hour, recovered at 4 hours, and was again depressed at the agonal stage. In addition, isoproterenol-stimulated cAMP production in ventricular slices from ETOX rats was attenuated by 3 hours after administration. These data suggest that myocardial beta-adrenergic receptor mechanisms are altered during endotoxicosis, which may account for reports of decreased functional responsiveness to catecholamines under similar conditions. At 1 hour after ETOX, adrenal NE did not change, but E was depleted and remained low throughout the period. By 2 hours, spleen NE was also found depleted. Myocardial NE did not change until the agonal stage, when it was severely depressed. This implies that there may be nonuniform activation (duration and/or intensity) of sympathetic pathways during endotoxicosis.