The gene expression of myeloperoxidase (MPO) in HL60 cells, as tested by Northern blot analysis with a MPO gene probe, was markedly suppressed at 9 h after the addition of gamma-interferon (IFN-gamma) (200 U/ml), whereas cytochemically detected MPO activity, cell surface antigen expression, and cell morphology remained unchanged even at 48 h. IFN-gamma of 50 U/ml was sufficient for the suppression at 24 h. When the HL60 cells treated with IFN-gamma (200 U/ml) for 24 h were cultured in the absence of IFN-gamma for another 24 h, the transcript of MPO gene reverted to a level comparable to that of the HL60 cells cultured thoroughly in the absence of IFN-gamma, indicating the reversibility of the suppression. The suppression of MPO expression at RNA level, probably independent of differentiation, is a biological activity exerted by IFN-gamma, which has not been previously reported.