T helper type 1 (T_H1) immune responses are central in cell-mediated immunity, and a T_H1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3–Ig) of both Tim-3 isoforms specifically bound CD4⁺ T cells, indicating that a Tim-3 ligand is expressed on CD4⁺ T cells. Administration of Tim-3–Ig to immunized mice caused hyperproliferation of T_H1 cells and T_H1 cytokine release. Tim-3–Ig also abrogated tolerance induction in T_H1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T_H1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.