Mice homozygous for either of the autosomal recessive mutations, lpr or gld, have a large number of abnormalities in common including marked expansion of an unusual subset of T cells that are Thy-1+, Ly-1+, Ly-2-, Ly4- and B220+. In spite of the fact that these cells express T cell receptors for antigen, they fail to respond to stimulation with alloantigens. Biochemical analyses of the T3/T cell receptor complex showed that all components were present as on normal T cells but they exhibited anomalous patterns of phosphorylation. Normal T cells stimulated with antigen or lectin exhibit phosphorylation of p21 on tyrosine and gp21 on serine. By comparison, for lpr and gld T cells the p21 component of T3 was phosphorylated in the absence of stimulation whereas the gp21 component of T3 was not. Studies devoted to cloning the gld gene have been initiated with the characterization of molecular clones located near the mutant gene on chromosome 1. Analyses of Ly-5 among inbred and wild strains of mice revealed 5 new alleles defined by serology and restriction fragment length polymorphisms.