Malignant melanoma and hypernephroma show marginal response to chemotherapeutics and interferons when used as single agents. Using a modified soft agar clonogenic assay we investigated the antiproliferative effects of combinations of vinblastine, bleomycin, adriamycin, interferon alpha and gamma. On the hypernephroma cell line combinations of bleomycin and adriamycin with interferon gamma as well as combinations of both interferon types resulted in a synergistic antiproliferative effect. On the melanoma cell line combinations of bleomycin and adriamycin with interferon alpha and combinations of vinblastine with interferon gamma acted in a synergistic manner. All other combinations tested were only additive. Thus far, we could not find any antagonistic effect of interferons and chemotherapeutics.