The potency of TCR signaling can regulate the differentiation of naive CD4+ T cells into Th1 and Th2 subsets. In this work we demonstrate that TCR signaling by low-affinity, but not high-affinity, peptide ligands selectively induces IL-4 transcription within 48 h of priming naive CD4+ T cells. This early IL-4 transcription is STAT6 independent and occurs before an increase in GATA-3. Furthermore, the strength of the TCR signal differentially affects the balance of NFATp and NFATc DNA binding activity, thereby regulating IL-4 transcription. Low-potency TCR signals result in high levels of nuclear NFATc and low levels of NFATp, which are permissive for IL-4 transcription. These data provide a model for how the strength of TCR signaling can influence the generation of Th1 and Th2 cells.