C-terminal Src Kinase (Csk) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases to inhibit their activities. To investigate the possible regulation of spermatogenesis by Src-Csk loop, the postnatal changes in the expression of Csk were examined in mouse testes. Semiquantitative RT-PCR analysis revealed that Csk mRNA increased during neonatal development and peaked at 2 weeks of age. Following the decrease during pubertal development, Csk expression re-increased in adult testes. In Western blot, immature testes showed higher expression of Csk protein than the pubertal or adult testes. In immature testis, Csk immunoreactivity was largely found in the Sertoli cell and there was no visible difference in the Csk immunoreactivity among the seminiferous tubules. In adult testis, however, a differential Csk immunoreactivity was found among the seminiferous tubules. Intense signal was found in the adluminal cytoplasm of the Sertoli cells bearing the post-meiotic differentiating germ cells, suggesting that Csk may participate in the remodeling of seminiferous tubule during late phase of spermatogenesis. Csk immunoreactivity was also found in the Leydig cells, suggesting the possible regulation of Leydig cell function. Src-Csk loop may participate in the differentiation of the seminiferous epithelia and Leydig cells in mouse testis.