This report shows that p53 gene expression is required for proliferation of Concanavalin A (ConA)-stimulated murine T lymphocytes. p53 gene-specific antisense oligodeoxynucleotides strongly inhibited expression of p53 gene in T lymphocytes, causing suppression of ConA-induced cell proliferation. In contrast, the complementary-sense oligomers had no inhibitory effects. Northern and immunoprecipitation-blotting assay data, however, showed no change in p53 mRNA and proteins synthesized in T lymphocytes before and after ConA stimulation. p53 proteins in the resting and ConA-stimulated T cells had different immunoreactivity with specific monoclonal antibodies. p53 from resting T cells only reacted with "wild-type form" p53-specific monoclonal antibody (PAb246); whereas, p53 from ConA-stimulated T cells was recognized by "mutant-form" p53-specific monoclonal antibody (PAb421). These results suggest that the conformation of p53 proteins in resting and ConA-stimulated T cells are different. The p53 conformation changes may be related to the regulation of murine T lymphocyte proliferation.