Male rats, 5 and 90 d of age, continuously inhaled 500 ppm CO [40% carboxyhemoglobin (COHb)] for 5.5-8.0 wk. Cardiomegaly and polycythemia developed as previously reported. Heart weight gain in young and old rats treated with CO was accompanied by increased cytochrome c content (nmol) in both left ventricle (LV) and right ventricle (RV) relative to controls. Cytochrome c concentration (nmol/g wet weight), however, was significantly depressed in LV and RV of young CO-exposed rats relative to controls, while there was no change in LV and RV of the old CO-exposed group. LV cytochrome c concentration was significantly higher than that of RV in both young and old, CO-exposed and control rats. On the other hand, cytochrome c concentration in young and old control LVs was similar, as was cytochrome c concentration in RVs of young and old control rats. Three additional experiments were carried out with 5-d-old rats inhaling 500 ppm CO, for 47 and 25 d. These also showed the increase in myocardial cytochrome c content and compromise of cytochrome c concentration, and both changes were greater with longer exposure.