The bronchodilator effects of aminophylline have been well documented but its effect on ventilatory drives has not been systematically evaluated. Accordingly, the ventilatory responses to hypoxia and to hypercapnia were measured before and after the intravenous administration of 5 mg of aminophylline per kg of body weight to 6 normal subjects. Hypoxic ventilatory response, as measured by an index of the relation between ventilation and hypoxia (parameter A) increased from a mean +/- SE control value of 146 +/- 25 to 254 +/- 35 75 min after the infusion (P less than 0.05). Significant increases in A were also noticed immediately after and 35 and 50 min after the aminophylline infusion. Oxygen consumption increased from a control value of 235 +/- 21 to 263 +/- 21 ml per min STPD (P less than 0.03), and CO2 production increased from 184 +/- 12 to 202 +/- 13 ml per min STPD (P less than 0.01) after aminophylline. Hypercapnic ventilatory response, measured as the slope of the ventilatory response to hypercapnia, was not altered after the aminophylline. Thus, in addition to bronchodilation, the augmentation of the ventilatory response to hypoxia may be a useful factor when this drug is used in acute respiratory failure secondary to airway obstruction.