The effects of whole-body hyperthermia (WBH) on the course of the Lewis lung carcinoma (LLC) and B16 melanoma (B16) were examined. WBH was generated by microwave (2450 MHz) at an intraperitoneal temperature of 39.5-40.0 degrees C and an intratumoral temperature of 40.0-40.5 degrees C for 30 min once a week, X 3 (LLC) or X 6 (B16). The mice were sacrificed 21 days (LLC) or 42 days (B16) after tumor implantation and lung metastases were scored. Natural killer (NK)-cell activity was determined against the YAC-1 tumor target in WBH-treated tumor-bearing mice as well as in tumor-bearing mice but untreated controls. The number of lung metastases was significantly reduced and NK-cell activity was higher in animals treated with WBH. Thus, this study suggests that WBH interferes with the spread of organ metastases, possibly through a mechanism involving NK cells.