T cell activation depends on appropriate and precise regulation of gene expression. Here we find that rapidly translocated RNA-binding protein HuR, forms messenger ribonucleoprotein (mRNP) complexes with transiently expressed mRNAs encoding early-response transcription factors, including c-Fos, c-Jun, and Egr-1. Knockdown and overexpression assays demonstrated that proper posttranscriptional control of Egr-1 expression requires HuR-mediated translation control. Further analysis showed that the Egr-1 3′UTR, which contains AU-rich elements (AREs) and interacts directly with HuR, suppresses reporter gene expression and mediates posttranscriptional regulation of Egr-1 by HuR. These findings underscore an essential role for HuR in regulating early events during T cell activation.