The potent alpha and beta adrenergic actions of epinephrine are probably mediated through an increase in free intracellular calcium concentration. Despite an absence of experimental evidence, many clinicians administer epinephrine with calcium to augment its cardiovascular effects. We evaluated the effects of calcium on epinephrine's pressor response in both normal and endotoxin-treated rats by administering epinephrine to animals made hypercalcemic with calcium chloride or hypocalcemic with the calcium chelator EGTA. EPI, given in incremental doses of 10, 20 and 50 micrograms/kg, produced incremental increases in mean arterial pressure. Calcium chloride infused i.v. at a rate of 50 mg/ml/hr significantly (P less than .05) blunted (50% decrease) the hypertensive response to 50 micrograms/kg epinephrine in normal animals. In endotoxin-treated rats, calcium chloride at 50 mg/ml/hr significantly blunted the hypertensive response to 10 micrograms/kg (73% decrease), 20 micrograms/kg (62% decrease) and 50 micrograms/kg (50% decrease) epinephrine. Endotoxemia plus calcium chloride at 25 mg/ml/hr also significantly blunted (30% decrease) the hypertensive response to 50 micrograms/kg EPI. By contrast, hypocalcemia produced by EGTA (30 mg/ml/hr) had no effect on epinephrine's hypertensive effects in normal or endotoxemic rats. Since calcium chloride significantly diminishes epinephrine's hypertensive effects in both normal and endotoxin-treated rats, the clinical use of calcium chloride along with epinephrine may not have a sound experimental basis.