Two human mesothelioma xenograft lines, BG and ES, serially passaged in athymic mice, were studied to determine the efficacy of .alpha.-interferon in this type of tumor. Treatment began after progressive tumor growth was established. Recombinant human .alpha.-interferon-2a (Roferon-A) was given by s.c. injection, at a site distant from the tumor, at a dose of 2 .times. 105 IU 5 days per wk for 5 wk. Mild inhibitory activity was noted in both lines with interferon alone, cis-Diamminedichloroplatinum(II) (CDDP) (4 mg/kg) weekly .times. 5 was effective in line BG, while mitomycin C (1.5 mg/kg) weekly .times. 3 was effective in line ES. CDDP was not as effective in line ES. The moderate activity of CDDP in line BG and of mitomycin C in line ES was markedly increased by the addition of .alpha.-interferon. The combination of mitomycin C and .alpha.-interferon was as effective as mitomycin C and CDDP. No additional toxicity was noted by the addition of .alpha.-interferon. The combination of recombinant human .alpha.-interferon-2a and active chemotherapeutic agents is effective in mesothelioma xenografts.