Mice carrying the lpr gene, SCG and MRL-lpr/lpr mice, were used to characterize the phenotype and lpr gene of abnormally proliferating T cells in these mice. A major population which expanded in these mice were T cells expressing intermediate (int) levels of T cell receptor (TCR) (and CD3) and the phenotype of interleukin-2 receptor (IL-2R) beta lo alpha- (possibly abnormal TCRint cells). The levels of TCRhi cells of thymic origin (generated through the mainstream of T cell differentiation in the thymus) profoundly decreased after the onset of disease. However, a small population of normal TCRint cells (i.e. IL-2R beta hi alpha-) were also found to exist in all tested organs. For example, the majority of abnormal IL-2R beta lo TCRint cells were CD4-8- CD2-, while normal IL-2R beta hi TCRint cells were a mixture of single-positive cells (mainly CD8+), CD4-8- cells and CD2+ cells. Moreover, normal TCRint cells preferentially produced normal Fas mRNA and Fas molecules from the lpr gene. This phenomenon explains the leaky appearance of normal Fas mRNA and Fas molecules in mice carrying the lpr gene. It is suggested that a small population of IL-2R beta hi TCRint cells are resistant to the lpr genetic abnormality.