Theophylline therapy increases left ventricular output in preterm infants by a combination of positive inotropic and chronotropic effects. The cardiovascular effects of caffeine were evaluated in 20 clinically stable preterm infants. Ten infants received intravenous caffeine citrate with a loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg every 24 hours, and 10 infants were control subjects. Left ventricular output, stroke volume, and heart rate were measured by using a combination of two-dimensional and pulsed Doppler echocardiography and mean arterial blood pressure by oscillometry (Dinamap, Critikon, Division of McNeil Laboratories, Irvine, Calif) before the start and on days 1, 2, 3, and 7 of caffeine therapy and 7 days after discontinuation of therapy. Compared with controls, left ventricular output and stroke volume were significantly increased on days 1 to 7 of caffeine therapy. Caffeine led to an increase in the mean arterial blood pressure on the first 3 days of therapy, but the heart rate did not change. These data indicated that caffeine administration leads to a significant increase in left ventricular output in preterm infants and that this inotropic effect is accompanied by a pressor effect.