It was hypothesized that manipulation of litter size, thus nutrition, which has been shown to alter the neonatal response to cardiovascular stress (i.e. carbon monoxide) might also alter persistent post-stress changes. Rat pups reared in litters of 4 and 16 inhaled 500 ppm CO for 32 days ("CO"), or served as controls ("AIR"). Some pups were killed at 14-15 days of age to assess initial cardiomegaly. As adults, right ventricle (RV) mass was greater in CO/4 males (123 days of age) and females (113 days of age) than in same sex CO/16 rats. Persistent RV cardiomegaly was present in CO/4 males and females compared to AIR's of the same litter size and sex, whereas this was the case only in females comparing CO/16 and AIR/16 rats. RV mass was significantly larger in AIR/4 males than in AIR/16 males. Plots of initial cardiomegaly (both ventricles) versus persistent cardiomegaly (RV) for large and small litters produced similar slopes for the two sexes, with females lying above males. Resting heart rate, monitored in males (66-121 days of age) and females (81-109 days of age), was increased by small litter size, and also by CO, particularly in the males. Resting heart rate was significantly correlated with RV weight. RV DNA content and concentration were increased by small litter size in the males, and concentration also by CO. The male CO/4 rats had the highest DNA content and concentration. In the females, DNA content was increased by small litter size and was greatest in the CO/4 group. Thus, the effects of small litter size have lasting effects: i.e. augmented persistent cardiomegaly, persistent tachycardia, and myocardial DNA content and concentration.