In the present study, we investigated whether tyrosine phosphorylation was involved in thymic involution, which has been reported to correlate well with the effects of various kinds of stresses. Immunohistochemistry using the anti-phosphotyrosine antibody showed that the immunoreactivity decreased remarkably in the involuted thymus of stressed rats as compared with the control thymus. Immunoblot analysis using the anti-phosphotyrosine antibody revealed the tyrosine-phosphorylated proteins with apparent molecular masses of 120, 90, and 70 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis were detected in the control thymus. The immunoreactive band corresponding to the three proteins decreased remarkably in the involuted thymus. Further, we found by immunoprecipitation experiments that the 120 kDa protein was p130cas, a crk-associated src substrate. These findings suggest that tyrosine phosphorylation signaling may be involved in thymic involution.