Monoclonal nonspecific suppressor factor (MNSF) is a lymphokine derived from a murine T cell hybridoma. The action of MNSF is mediated by specific cell-surface receptors. Since IFN-gamma alters the cellular response to MNSF (M. Nakamura, H. Ogawa, and T. Tsunematsu, J. Immunol. 138, 1799, 1987), we investigated whether IFN-gamma has an effect on the expression of MNSF receptor on target cells. IFN-gamma enhanced the expression of MNSF receptor on both MOPC-31C cells (a murine plasmacytoma line) and EL4 (a murine T lymphoma line). Incubation with IFN-gamma increased the number of specific MNSF-binding sites by about 50 to 90%, with no significant change in binding affinity. IFN-alpha and IFN-beta also increased MNSF binding, although the effect of the saturating amounts was lower than that seen with IFN-gamma. Maximal enhancement of receptor expression was observed after about 15 hr of incubation with IFN-gamma. No demonstrable change occurred in the kinetics of internalization of 125I-MNSF bound to MOPC-31C cells preincubated without or with IFN-gamma.