Effects of hyperthermia (42.5 degrees C) and gamma radiation (30 Gy) on ADP-ribosyl transferase, NAD+, and ATP pools in human mononuclear leukocytes have been investigated. It was found that the gamma-ray activation level of the enzyme was not influenced by this hyperthermia for 45 min. Following deprivation of ATP synthesis by 2,4-dinitrophenol, an uncoupler of the oxidative phosphorylation, and omitting glucose from the culture medium, the NAD+ pool was reduced to about 60% of control value. The potentiation of ATP production by exogenously supplied adenosine was reduced after a combined treatment of the cells with hyperthermia and gamma radiation. Mitochondrial and endoplasmic changes within the mononuclear leukocytes were also observed. Based on these findings a model for the hyperthermia effect is proposed.