We have previously described a monoclonal antibody (mAb), CZ-1, which reacts with an epitope expressed on most peripheral basophils, natural killer cells, B cells, and CD8+ T cells, but not with most thymocytes or peripheral CD4+ T cells. Here we show that mAb CZ-1 defines a sialic acid-dependent epitope associated with a subpopulation of CD45 molecules. This conclusion is based on the ability to block binding of mAb CZ-1 by sialic acid, neuramin-lactose, neuraminidase, and mAb to CD45RB, and by expression of the epitope on transfected psi 2 cells expressing exon B of CD45. The results suggest that the CZ-1 epitope is a post-translational modification expressed on a subpopulation of the CD45 molecules also expressing the B exon. Expression of the CZ-1 epitope was required for freshly isolated lymphocytes to respond to interleukin-2 (IL-2). Depletion of CZ-1+ cells by C' or by cell sorting of thymocytes or splenocytes eliminated the IL-2 responsive cells. The subpopulations of thymocytes and CD4+ splenocytes responding to IL-2 were exclusively within the small CZ-1+ subpopulation. mAb CZ-1 was also used to subdivide CD45+ and CD45RB+ splenocytes into IL-2-responsive and -nonresponsive subpopulations. The CZ-1 epitope was also expressed on virtually all lymphokine-activated killer cell precursors. These data, thus, indicate that cells responsive to IL-2 express this sialated modification of CD45.