Organotypically cultured, confronting pairs of B16B16 cell clusters and fragments of embryonic chick or mouse heart, as used for the study of invasion in vitro, were treated with murine TNF plus IFN-gamma for 4 and 7 days. This treatment selectively killed the B16B16 cells and left the heart tissue intact as assayed by histology and by plating confronting pairs and spent medium on tissue culture substrate. Using this organ culture assay, which more closely mimics the situation in vivo, we confirmed the tumor-selective cytotoxic effects of combined treatment with TNF and IFN-gamma as observed in separate cultures of malignant and non-malignant cells on "artificial" substrate.