SummaryHuman polymorphonuclear leucocytes (PMN) are thought to be immunosuppressive. The suppressive mechanism(s) used by PMN are, however, not well defined and in this study they were analysed using T-cell responses to CD3 + CD28 monoclonal antibodies (mAb) as a readout. We demonstrate that in vitro activated PMN (PMN act ) can, without any T-cell interaction, induce apparent T-cell suppression by inhibiting the stimulatory capacity of the CD3 mAb. However, a cell-directed suppression of Tcell proliferation was observed when PMN act were added to pre-activated T cells that are already committed to polyclonal proliferation. This suppression was partially reversed by catalase addition (P < 0Á01) and largely reversed by addition of exogenous interleukin-2 (P < 0Á001) but was not significantly reduced by nitric oxide synthase inhibition, myeloperoxidase inhibition or addition of excess arginine. Following removal of PMN act , suppressed T cells could respond normally to further stimulation. In addition to suppressing proliferation, co-culture with PMN act also induced a significant decrease in T-cell viability that was reversed by catalase addition (P < 0Á05). The addition of the arginase inhibitor N-hydroxy-nor-L-arginine induced both a further significant, catalase-sensitive, loss in T-cell viability and increased nitrite release (P < 0Á001). These data demonstrate that PMN, when activated, can both induce T-cell death and reversibly inhibit proliferation of activated T cells. The mechanisms underlying these distinct processes and the effects of arginase inhibitors on PMN induced cytotoxicity merit further investigation.