The effects of physiologically relevant hypoxia on the catalytic activity of cytochromecoxidase (CytOX), mito-chondrial gene expression, and both nuclear and mito-chondrial encoded CytOX mRNA levels were investigated in murine monocyte macrophages, mouse C2C12 skeletal myocytes and rat adrenal pheochromocytoma PC12 cells. Our results suggest a coordinated down regulation of mito-chondrial genome-coded CytOX I and II and nuclear genome-codedCytOX IV andVbmRNAs during hypoxia.