Numerous immunomodulatory effects are caused by propanil, an extensively used postemergent herbicide. The T-dependent antibody response is suppressed after exposure to propanil, raising the question of propanil's effect on T-helper-cell populations. In the present study, we show that the production of several T-cell cytokines is affected by propanil after in vivo or in vitro exposure. In vivo exposure to propanil caused the reduction of interleukin (IL)-2, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-gamma production in concanavalin A-stimulated spleen cell cultures established 2 d after exposure. IFN-gamma and GM-CSF production had recovered by d 4 postexposure; however, IL-2 and IL-6 levels continued to be depressed through d 7 postexposure. Continuous in vitro treatment of normal spleen cells with propanil decreased IL-2, IL-6, GM-CSF, and IFN-gamma production after concanavalin A activation. Pulsing normal spleen cell cultures with propanil for up to 8 h before T-cell activation resulted in reduced IL-6 but not IL-2 or IFN-gamma production. These data indicate that propanil can selectively inhibit spleen cell cytokine production, which could contribute to the immunomodulatory effects previously described.