Liposomes containing the extract of trinitrophenylated (TNP) epidermal cells stimulated lymph node cells from TNCB-sensitized mice effectively. Optimal stimulation was achieved by the liposome containing 0.06 microgram of the extract of TNP epidermal cells/microgram of phospholipid at a concentration of 20 micrograms phospholipid/ml. The response was hapten-specific and macrophage-dependent. UV irradiation of the epidermal cells abolished their ability to stimulate the lymph node cells. Furthermore, the liposomes containing the extract of TNP epidermal cells treated with anti-Ia and complement failed to stimulate the lymph node cells. The liposomes recovered their reactivity when nonhaptenated Ia antigen-rich epidermal extract was added. Taken together, it is likely that haptenated molecules and Ia antigen on the liposome stimulated T-lymphocytes in the presence of macrophages.