The cytotoxic T cell line CTLL-2 and the T helper cell line HT2 proliferative in response to interleukin 2 (IL-2) or IL-4 without requiring stimulation by antigen through the T cell receptor and therefore lend themselves for studies of IL-2 and IL-4-dependent proliferation and signalling through their cognate receptors. Here we have used CTLL-2 and HT2 cells to investigate the effect of the inflammatory mediator prostaglandin E 2 (PGE 2 ) on IL-2- and IL-4-dependent proliferation. PGE 2 inhibited IL-2- as well as IL-4-dependent proliferation of both CTLL-2 and HT2 cells, with IL-4-dependent proliferation being more sensitive than IL-2-dependent proliferation and CTLL-2 cells being more sensitive than HT2 cells. A quantitative dose–effect analysis revealed a two-step increase of inhibition (around 10 −10 M and 10 −5 M PGE 2 ) for all combinations of cells and cytokines approaching 100% at high concentrations of PGE 2 . The data suggest that even in cases where synthesis of IL-2 and IL-4 is differently affected by PGE 2 , IL-2- and IL-4-dependent T cells may still be similarly sensitive to PGE 2 by way of their cytokine responsiveness. Furthermore, the effects of PGE 2 may be mediated by more than one functional binding site or receptor subtype. PGE 2 levels are an important consideration when CTLL-2 and HT2 cells are used for the measurement of IL-4 and IL-2.