The distribution of the alpha 6 subunit of integrins in the development and sexual differentiation of mouse testis was analyzed by light and electron microscopy during the embryonic, fetal and early postnatal periods. At the pregonadal phase only the epithelial cells of the mesonephric duct and of the distal mesonephric tubules showed a reaction to alpha 6, whereas the surface epithelium and the mesenchyme of the mesonephros were negative or contained only a rudimentary amount of the alpha 6 subunit. With the formation of the gonadal ridge and the testicular blastema, the gonadal cells became positive for the alpha 6 subunit. This expression remained in embryonic cord cells and in the vascular endothelial cells, whereas the differentiating cells of the surface epithelium, tunica albuginea, the Leydig cells, and the interstitial mesenchymal cells were negative. With the fetal and postnatal differentiation, the expression of the alpha 6 subunit gradually diminished in the cord cells, and by the prepubertal phase, alpha 6 was found only at adhesion sites between some Sertoli cells. Similar changes were seen in the mesonephric duct and tubules, and in the rete cords. The presence of alpha 6 in regions undergoing developmental cell aggregation processes and their disappearance during tissue maturation, suggest that alpha 6 plays a specific but transient role in gonadal cell adhesion necessary for the histogenetic organization of the testis. In addition to its role in developing and organizing cells, alpha 6 integrin was also a prominent component in degenerating cells.(ABSTRACT TRUNCATED AT 250 WORDS)