Gamma radiation activates protooncogenes that are involved in early signal transduction, e.g., Raf‐1. Most studies of effects of gamma radiation on lymphocytes deal with regulation of gene expression. However, early surface receptor expression in response to radiation has not been reported. We studied the effect of radiation on lymphocyte CD69 expression and BrdU uptake in the absence or presence of phytohemagglutinin (PHA). Radiation induces CD69 expression on T and B cells in a dose‐ and time‐dependent manner. Four hours after a dose of 906 cGy, approximately 90% of B and 12% of T cells express CD69. CD69 expression diminishes after 6 h and requires de novo protein synthesis and protein phosphorylation. Radiation alone does not stimulate cell proliferation, as measured by BrdU incorporation, at any radiation dose tested. Furthermore, radiation enhances PHA induced CD69 expression at 2 h, but inhibits BrdU incorporation at day 3 in a dose‐dependent fashion. CD69 functions as a marker for response to radiation, but unlike antigen or mitogen, radiation‐induced CD69 expression does not lead to proliferation. Cytometry 30:304–312, 1997. © 1997 Wiley‐Liss, Inc.