Peripheral blood mononuclear cells (PBMC) from nonatopic donors sensitive to Mycobacterium tuberculosis purified protein derivative (PPD) and from atopic donors sensitive to PPD and house dust mite antigen (HDM), were stimulated in vitro to proliferate in response to exogenous IL-2. In the presence of exogenous IFN-gamma, the response of cells from atopic donors to PPD was either unaffected or slightly enhanced, whereas the response to HDM was inhibited in a dose-dependent manner. The response of cells from nonatopic donors to PPD remained unchanged or was only slightly inhibited and this was not dose-dependent. Exogenous IL-4 did not reverse the inhibitory effects of IFN-gamma and a neutralizing antibody to IL-4 did not inhibit the proliferative response of cells to HDM and IL-2. Dexamethasone inhibited the IL-2-mediated response of cells from atopic donors stimulated with HDM, whereas the IL-2-mediated response of cells induced by PPD was either unchanged or stimulated by dexamethasone. Cyclosporin A inhibited the response of cells to both HDM and PPD. These results suggest that IFN-gamma can exert a selective effect on the response of T lymphocytes to different antigens and that it is possible to identify compounds able to regulate this activity.