Currently, the combination of hyperthermia with a variety of chemotherapeutic agents and cytokines for the treatment of disseminated human malignancy is being examined. In this study we investigated the effects of 41 degrees-42 degrees C whole-body hyperthermia (WBH) and the cytokine interleukin-1 (IL-1) on cytochrome P450 in mice. At 24 h following 1 h of 41 degrees-42 degrees C WBH, IL-1 or combined treatment, hepatic microsomal cytochrome b5 and aminopyrine N-demethylation were assayed. Cytochrome b5 activity was not significantly diminished by WBH, IL-1 or WBH + IL-1, but N-demethylation was suppressed by the combination of WBH + IL-1 and, to a lesser extent, by WBH alone.