We have studied the effects of interferon (IFN)-alpha, beta, and gamma in vitro on the growth and invasive potential of human melanoma SK-MEL-118 cells. The antiproliferative effects of IFNs were assessed by a quantitative regrowth assay in which cells were treated with IFNs at concentrations of 10(2), 10(3) or 10(4) IU/ml for 3 days (until day 4) and then further incubated without IFNs for 7 days (until day 11). The growth inhibitory effect of each IFN on melanoma cells was dose- and time-dependent. Among these three types of IFNs, however, IFN-beta exerted the strongest inhibitory effect on cell growth. To assess the anti-invasive effect of each IFN on melanoma cells, we employed an in vitro assay system using matrigel-coated Transwell chambers. When cells were treated with 10(2), 10(3), or 10(4) IU/ml of the three types of IFNs for 24 hours, the amount of tritiated thymidine incorporated into melanoma cells were treated for 24 hours with 10(4) IU/ml of IFN-beta or gamma prior to the assay, the number of cells that invaded the filter decreased by 40%; this decrease was only 10% with the same amount of IFN-alpha. Simultaneous addition of IFNs during the invasion assay was not effective in any combination. Only when the cells were pretreated with IFNs, antiinvasive effects against melanoma cells were exerted. IFN-alpha was less inhibitory than IFN-beta or gamma on proliferation and not at all inhibitory on invasion. Considering both the antiproliferative and antiinvasive effects of IFNs, our results suggest that IFN-beta has the strongest antitumoral effect on human melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)