The purpose of this study was to determine whether the formation of hapten-specific suppressor T lymphocytes induced by the epicutaneous sensitization of UV-irradiated mice could suppress other hapten-specific immune responses in addition to contact hypersensitivity (CHS). Suppressor cells were induced by applying trinitrochlorobenzene (TNCB) to the unexposed skin of mice irradiated several days earlier with 40 kJ/m2 UVB (280-320 nm) radiation. Previous work demonstrated that the spleens of such animals contain Lyt-1+, 2-T lymphocytes which prevent the induction of CHS to TNCB when transferred to normal mice, and inhibit proliferation of normal lymphocytes in vitro to TNP-modified syngeneic cells. These studies show that addition of T lymphocytes from UV-irradiated, TNCB-sensitized mice to cultures of normal lymphocytes and TNP-modified syngeneic cells inhibited the generation of TNP-specific cytotoxic T lymphocytes (CTL). The inhibition was dose-dependent and occurred only when the suppressor cells were present during the first 24 hr of culture. The suppressor cells had no effect on the activity of preformed CTL. In addition, injection of the suppressor lymphocytes into mice at the time of i.v. injection of TNP-modified sheep red blood cells (TNP-SRBC) reduced the number of direct plaque-forming cells against TNP, but had no effect on the production of antibody against SRBC. Cells that inhibited anti-TNP antibody formation were Thy-1+, Lyt-1+, 2-. These results indicate that hapten-specific suppressor cells from UV-irradiated mice prevent the activation of several different hapten-specific immunological pathways.