In the male CD-I mouse submandibular gland (SMG) renin activity increases markedly with puberty. We have reported that this is, in part, due to an androgen-mediated increase in renin gene transcription. In this study, we examined whether posttranslational processing is also influenced by androgen. We studied secretion and processing of active renin in the CD-I male mouse SMG which secretes primarily the Ren-2 renin isozyme before and after puberty and also compared findings with the adult female CD-I mouse. Maturation increases renin level and secretion rate in the male SMG but much less in the female, In addition, Western blot analysis of molecular forms of renin in SMG tissue and media shows a predominance of 1-chain intermediate form of renin before puberty but of the 2-chain mature form thereafter. Adult female SMG contains and secretes much less active renin than the male organ. Administration of testosterone to the female CD-I mouse induces an adult male level and pattern of secretion, with high concentrations of active 2-chain renin being secreted. These data suggest that SMG renin is androgen regulated, in part by an androgen-responsive enzyme that processes 1-chain renin to the 2-chain form.