Antigen-specific murine CD4+ T cell clones can be divided into functionally distinct subsets known as Th1 and Th2. To date these cells have been indistinguishable by surface phenotype. This report identifies two anti-CD45R monoclonal antibodies (14.8 and C363.16A) that bind preferentially to Th2 cells. Further analysis of the CD45-specific mRNA in Th1 and Th2 cells shows clear differences between these two cell types. Th1 cell clones express mRNA for the two smallest forms of CD45 containing none or only one of the alternatively splices exons. In contrast, Th2 cell clones express predominantly the high molecular weight isoforms of CD45 containing two or three of the alternatively spliced exons.