We studied the growth effects of human recombinant interferon (IFN)-alpha-2 and -gamma on various human cell lines. Four cell lines from solid tumors (WiDr, CCL 185, BT 20, KB) and three cell lines from hematologic malignancies (U 937, U 266, MOLT 4) were chosen. The study was performed using two different assays: (1) a soft agar cloning assay, and (2) a monolayer and suspension culture. In the soft agar assay alpha-IFN inhibited colony growth of 6/6 lines tested (the line MOLT 4 could not be plated); in the monolayer assay it inhibited proliferation of 6/7 lines tested. Gamma-IFN showed inhibitory effects on 5/6 cell lines tested in the soft agar assay, but on one line (CCL 185) low concentrations of gamma-IFN led to a significant increase in the number of colonies. Using the monolayer assay, gamma-IFN showed inhibition of 6/7 lines tested, whereas a stimulation of growth could not be observed. With a combination of alpha- and gamma-IFN, synergistic effects were seen on a histiocytic cell line (U 937) in both assays and a marginal synergism on the T-cell line MOLT 4 in the monolayer assay.