The effect of selective and nonselective beta-adrenoceptor blockade on the thermoregulatory responses of 11 physically active, healthy, young adult men was studied during 2-hour block-stepping in heat. The trial consisted of 3 periods of 6 days each during which propranolol (160 mg/day), atenolol (100 mg) or matching placebo was administered in a randomized, double-blind crossover fashion. Propranolol and atenolol induced similar, significant (p less than 0.001) increases in subjective ratings of perceived exertion. The mechanism of this increased fatigue was not evident from the documented alterations in serum electrolyte, blood glucose and blood lactate levels or ventilatory parameters. Propranolol did, however, induce a postexercise delayed serum-potassium reversion. Although rectal and mean skin temperature responses were essentially unaltered by beta-adrenoceptor blockade during block-stepping, an increased total sweat loss was observed with propranolol (p less than 0.01 versus placebo) and to a lesser degree with atenolol (p = not significant versus placebo). This indicates that persons receiving beta-adrenoceptor blockers have an increased need to adhere to a strict fluid-replacement regimen during exercise. This potentially adverse response was minimal with atenolol in contrast to propranolol, and this in turn suggests the use of beta1-selective adrenoceptor blockers during prolonged exercise when adequate fluid replacement is not possible.