Effects of human recombinant-DNA derived interferon-gamma and -alpha 2 on the adhesion of cultured breast cancer cells (BT-20, ZR-75.1, MCF-7, 734-B and Hs-578-T), larynx carcinoma cells (HEP-2), epidermoid carcinoma cells (KB), lung carcinoma cells (CCL 185), and ovarian carcinoma cells (1847) to the surface of cell culture plastic dishes were studied. Layered cells were detached after a 3-day treatment with interferon either by trypsin-EDTA, trypsin, protease or cooling to 4 degrees C. Treatment with interferon-gamma (500 unit/ml) significantly increased the incubation time for trypsin-EDTA, EDTA and at 4 degrees C necessary to bring cells into suspension for the 4 cell lines BT-20, ZR-75.1, MCF-7 and HEP-2. Interferon-alpha 2 was not able to induce a similar effect. Reattachment of interferon-gamma treated ZR-75.1 cells was not increased after harvesting by trypsinization or EDTA action. Decreased adhesion of cultured cells is associated with transformation and the effects of interferon-gamma may be explained by reinforced normal phenotype. Interferon-gamma induced adhesion was not associated with other interferon effects especially the anti-proliferative activity or modulation of surface antigens.