The ventilatory responses to catecholamine infusions have been well studied. Increases in plasma levels of cortisol and glucagon during stress may exert a synergistic effect with epinephrine. We examined the effect of epinephrine and a combined hormone infusion in four normal postabsorptive subjects. On three separate occasions each subject was assigned randomly to receive a 5.5-h infusion of saline (control), epinephrine (1.2 micrograms/m2 . min), or epinephrine plus cortisol (5 mg/m2 . min) plus glucagon (3 mg/kg . min). Oxygen consumption (VO2), CO2 production, minute ventilation (VE), tidal volume (VT), frequency (f), inspiratory flow, and inspiratory time during room-air breathing and inhalation of 2% and 4% CO2 were measured before infusion and during the last 2 h of infusion, using a noninvasive canopy system. VO2 increased significantly (p less than .05) from the control condition during both combined and epinephrine infusions (23% and 11%, respectively). The increase in VE was related linearly to the increase in VO2, and was primarily due to an increase in VT; however, there was a small rise in f. The VE-PaCO2 regression during CO2 inhalation was shifted leftward to an equal degree during both infusions. These data indicate that cortisol and glucagon augment the calorigenic action of epinephrine; ventilatory effects are augmented in relation to the changes in VO2.