To determine the factors regulating cardiac output in newborn lambs and to examine the effects of age after birth, we altered heart rate, afterload, preload, and myocardial contractility in eight younger lambs, 5 to 13 days old, and seven older lambs, 15 to 36 days old. To control heart rate, we ablated the atrioventricular node by injecting formalin into the region of the node, and paced the right ventricle at a baseline heart rate of 200 beats/min. After the lambs recovered from surgery, we performed two protocols. In the first protocol we assessed the effects of changing heart rate by pacing the ventricle at various rates. We also examined the effect of altering afterload and preload at a fixed heart rate: afterload was increased by infusing phenylephrine and decreased by infusing nitroprusside. Preload was increased by infusing blood or 0.9% NaCl solution over 2 min. In the second protocol, we increased myocardial contractility by infusing isoproterenol at a fixed heart rate. Increasing heart rate above baseline levels caused no significant increase in cardiac output in the younger lambs (3.9 +/- 4.0%, mean +/- SD), and only small increases in the older lambs (11.4 +/- 6.7%). Decreasing heart rate, however, resulted in a progressive decrease in cardiac output in both groups of lambs. Decreasing afterload caused no significant increase in cardiac output in the younger lambs (1.4 +/- 14.0%) and only a small increase in the older lambs (11.1 +/- 1.9%).(ABSTRACT TRUNCATED AT 250 WORDS)