To explore the effect of persistent cardiomegaly on cardiovascular function, groups of newborn rats inhaled up to 500 ppm CO for 33 days, after which development continued in ambient air. In the first two experiments hemodynamics were assessed by use of an anesthetized open-chest preparation; in the third experiment heart rate (HR) and arterial systolic blood pressure (BP) were monitored by auscultation in the conscious state. In all three experiments weights of left ventricle (LV) plus interventricular septum (S), both ventricles (2V), and right ventricle (RV) were significantly greater by prediction on the basis of body weight (BW) than for normal rats at 87-97, 166-176, and 337-339 days of age in females and 98-108, 177-183, and 337-339 days of age in males. 2V/BW ratio was significantly greater than littermate controls in all six instances. In all but one case (male, 177-183 days) the RV/(LV+S) weight ratios were significantly greater than the respective control groups. In experiments 1 and 2 unconscious HR was significantly elevated in females at 87-97 days and in males at 98-108 and 177-183 days. The first derivative of LV pressure rise was also increased. There was no significant change in BP or other hemodynamic parameters. In experiment 3 awake HR was elevated above controls in previously CO-treated males and females at six monitoring points between 78 and 200 days, whereas BP was not altered. BW of previously CO-exposed males was depressed and returned to normal only after 290 days. A similar decrement in BW was not seen in females. Neonatal CO inhalation and cardiomegaly causes persistent cardiomegaly and tachycardia, lasting a significant fraction of the maximal life span of the rat in both sexes.