Effects of human natural interferon alpha (nIFN) alone, human natural tumor necrosis factor alpha (nTNF) alone and their combination (OH-1) were tested on three human mesothelioma lines implanted in nude mice. Tumors were transplanted subcutaneously by trocar on treatment day -12. nIFN was given intraperitoneally (i.p.) at a dose of 2 x 10(7) or 2 x 10(8) IU kg-1 day-1, 5 days a week for 3 weeks. nTNF was given i.p. at a dose of 2 x 10(7) or 2 x 10(8) U kg-1 day-1 in the same schedule as that of nIFN. Tumor diameters were serially measured and tumor volumes were calculated. Antitumor effects were assessed by two methods: comparison of final tumor volumes in treated and control groups (T/C), and changes in median average total tumor volume. The treatment produced no clinically discernible toxicities. nIFN had strong inhibitory activity against all three human mesothelioma lines. nTNF alone had modest activity only at the high dose used. The combination of the two produced activity essentially similar to that produced by nIFN alone. High-dose nIFN may have a role as an active agent in the treatment of patients with mesothelioma.