Pulmonary metastases of a weakly immunogenic methylcholanthrene-induced murine fibrosarcoma MCA-106 were treated on day 10 for 10 days with saline, interleukin-2 (IL-2), hybrid recombinant interferon A/D (rIFN A/D) or the combination. IL-2/IFN effected > 99% reduction in tumor compared to saline, IL-2 or IFN alone. However, IL-2/IFN also resulted in early ( 150 days). Interruption of the 10-day treatment with a 2-day rest at 5 days abrogated early mortality, but despite significant prolongation of survival, no long-term survivors were seen. These data suggest possible clinical application of IL-2/IFN in the treatment of advanced tumor metastases but cautions of increased treatment toxicity associated with this regimen.