Although there are a number of physiological states associated with an increase in body temperature, eg, nonseptic and septic fever or exercise, the effects of hyperthermia on intermediary metabolism in vivo have received little attention. The current study was undertaken to examine the peripheral metabolism of ammonia and ammonia-related amino acids using a model of exogenously induced mild hyperthermia in nonfebrile subjects. Arteriovenous levels of metabolites were measured in subjects with known cerebrovascular insufficiency. Peripheral exchange of these metabolites was monitored before, during, and after hyperthermia to an average temperature of 38.5 degrees C. All subjects showed an increase in plasma ammonia and glutamate. There was also an associated peripheral production of ammonia and an uptake of glutamine and alanine by the skeletal muscle tissues. The exchange of glutamate was not affected. These findings indicate that hyperthermia is associated with a nitrogen-sparing effect, the mechanism of which is yet unknown.