The antitumor effect of recombinant human interferon-gamma (rIFN-gamma) and adriamycin (ADM), alone or in combination, against a human colon cancer cell line (RPMI 4788) was examined in vitro and in nude mice. In the in vitro study, antiproliferative activities of ADM were augmented additively or synergistically by combination with rIFN-gamma in a dose-dependent manner. Growth of RPMI 4788 cells (2 X 10(6)/mouse) transplanted subcutaneously into CD-1 nu/nu nude mice (day 0) was not inhibited significantly by 28 daily injections from day 10 of rIFN-gamma alone, but the antitumor effect of ADM was augmented synergistically by the simultaneous injection of rIFN-gamma. In an experimental model of pulmonary metastasis, in which RPMI 4788 cells (2 X 10(6)/mouse) were inoculated intravenously into BALB/c nu/nu nude mice (day 0), 10 or 21 daily injections from day 2 of rIFN-gamma alone had significant inhibitory effects against pulmonary metastasis in a dose-dependent manner. Furthermore, the inhibitory effect of ADM was augmented synergistically by daily injections of rIFN-gamma.