PRA and the inactive renin which is activated by cold (IR-C) were studied in a group of normal subjects and in patients with diabetes mellitus with and without the presence of nephropathy. The amount of renin activity, as measured after incubation of plasma at -5 C for 4 days, was called cold renin activity (CR. PRA was measured by a standard method. The difference between CR and PRA was used as a measure of IR-C. CR and PRA measurements were made on a normal salt diet, on a low salt diet, and after the administration of furosemide. In all three groups, CR and PRA were higher after salt depletion and following the administration of furosemide. A moderate but significant increase in IR-C was observed with these maneuvers in both groups of diabetes but not in normals. PRA and IR-C varied under different experimental conditions independent of each other. Although both PRA and IR-C were correlated with CR, no correlation was observed between PRA and IR-C. These findings suggest, although they do not prove, that the inactive renin is not a precursor of active renin. CR and IR-C were not significantly different between groups. PRA in patients with uncomplicated diabetes mellitus was normal or slightly high, whereas it was suppressed in patients with diabetes mellitus and nephropathy. The mechanism of suppressed PRA in patients with diabetes mellitus is not clear and may be related to the onset of renal disease itself.