We have examined a correlation between an expression level of poly(ADP-ribose) synthetase gene and the stage of monocytic differentiation. We selected three human leukemia cell lines, U937, THP-1, and J111, whose differentiation stage was characterized by nitroblue tetrazolium reduction activity, non-specific esterase activity, phagocytic activity and a cell surface marker. Enzyme activity and mRNA level of the synthetase decreased in accompaniment with the progress of monocytic differentiation. When THP-1 cells were treated with either interferon-gamma or phorbol ester, mRNA level of the synthetase decreased and HLA-DR or interleukin-1 was induced, respectively. We transfected expression plasmid of the exogenous synthetase gene to examine whether the down-regulation of the synthetase is a necessary step to induce these proteins. An expression of the exogenous synthetase gene inhibited the interferon-gamma- and phorbol ester-dependent induction of HLA-DR and interleukin-1. The results suggest that down-regulation of the synthetase may be a signal mediator of immunological response such as HLA-DR or interleukin-1 production in monocytes.