To test the relationship between hypoxia/ischemia tolerance and metabolic rate in neonatal tissues, isolated unperfused hearts of neonatal, juvenile, and adult mice were studied by microcalorimetry and microrespirometry. Additionally, microslices of mouse hearts were prepared and studied in a microcalorimeter under different oxygenation conditions. Neonatal hearts had a slower hypoxic/ischemic decline in heat output than adult organs, correlated with a higher uptake of physically dissolved oxygen from the incubation solution. In the slice experiments, the neonatal samples were found to exhibit a higher metabolic activity which enables them to maintain, at low pO(2), a similar metabolic rate as the adult tissue at high pO(2). This corresponds to the fetal adaptation to low intrauterine oxygen tensions and might be a common basis for the elevated neonatal hypoxia/ischernia tolerance as well as for the postnatal increase in metabolic rate up to the level to be expected from body size.