The biosynthesis of renin in the mouse submaxillary gland was defined using both cell-free translation and pulse-labelling methods. Renin is synthesized as a preproform and cleaved by microsomes to the proform. Prorenin (MW = 46 kilodaltons, pI 6.35) is processed intracellulary into an intermediate form (MW = 41 kilodaltons). The latter is converted by a slow intracellular process to the final major storage form (MW = 37 kilodaltons). Both the intermediate and the 37 KD forms are secreted. The biosynthetic precursor does not bind to pepstatin-aminohexyl sepharose. In parallel experiments, using rapid tissue extraction with buffers containing protease inhibitors and fractionation with affinity chromatography, we have also identified in the mouse submaxillary gland an inactive form of renin which has a MW of 48 2 KD and pI of 6.4. Mouse submaxillary gland inactive renin binds to affigel-blue and not to pepstatin-sepharose. The similarity in the properties of inactive renin and the biosynthetic renin precursor lends further support to the suggestion that tissue inactive renin may be the renin precursor.