Exogenous ATP (in combination with MgCl2) and creatine phosphate (CrP), were administered i.v. to E. coli endotoxin-shocked cats. Untreated shocked cats exhibited systemic hypotension during the 1st h and again from 4 h. Cardiac output fell progressively, and markedly elevated arterial lactate levels were evident within 1 h of endotoxin administration. Treatment with ATP (10 mg/kg every 30 min) during shock led to rapid hemodynamic deterioration in all cats; most of the cats were dead before completion of dosing (at 3 h). Long-lasting systemic hypotension and bradycardia were associated with this ATP administration and marked hypoglycemia developed in the survivors. Neither ATP (62 mg/kg) administered before endotoxin, nor CrP (500 mg/kg; administered either prior to endotoxin, or 1 h afterwards) significantly modified the hemodynamic or metabolic changes associated with endotoxin shock in this species. Neither ATP nor CrP increased survival (assessed at 5 h). Improved survival from shock with ATP treatment was previously demonstrated. There may be species differences in the responsiveness to exogenous ATP or, alternatively, a difference in the role of high-energy phosphates in different types of shock.