gal-1 is a modulator of thymocyte-fate decisions with opposing activities. By enforcing agonist ligand binding to the TCR, gal-1 promotes fast and transient activation of ERK and negative selection of autoreactive thymocytes, while permitting the generation of regulatory CD8αα IELs. In contrast, gal-1 expression antagonizes ERK signaling in thymocytes undergoing partial agonist-driven positive selection.