The cardiovascular effects of theophylline were studied in 11 clinically stable preterm infants. Theophylline was given as aminophylline using a loading dose of 6.8 mg/kg and a maintenance dose of 2 mg/kg every 8 hours intravenously. Cardiac output, stroke volume, and heart rate were measured using a combination of pulsed Doppler ultrasound and M-mode echocardiography. Compared with day 0, an increase was found in both cardiac output (P less than 0.01) and stroke volume (P less than 0.02) on days 1, 2, and 3. By day 7, stroke volume was comparable to pretreatment values, whereas cardiac output was still increased. Heart rate was augmented significantly (P less than 0.01) throughout the treatment period. Mean arterial blood pressure did not change. All but one of the neonates had serum theophylline concentrations between 6 and 13 mg/L. We conclude that both inotropic and chronotropic effects are evident during the first days of theophylline therapy. The metabolic cost of the increased cardiac output in the preterm infant with theophylline therapy deserves further attention.