Urinary kallikrein was measured in rats bred to be susceptible (S) or resistant (R) to the hypertensive effect of salt. To determine kallikrein, three different methods were used: (1) a new direct radioimmunoassay (RIA) for the enzymic protein: (2) a method based on the capability of kallikrein, when incubated with kininogen, to generate kinins which were then measured by RIA (kininogenase activity); and (3) a method based on the capability of kallikrein to break the ester bond of p-tosyl-L-arginine methyl ester (HCl (TAMe). A significant correlation ( r = 0.90) was found between the direct RIA and the kininogenase method. It was found that urinary kallikrein was significantly decreased in the S as compared to the R rats by the use of these three methods. Urinary kallikrein in the S rats was much lower when measured by the kininogenase method than by direct RIA or esterolytic assay. This difference could be due to excretion of pre-kallikrein and/or kallikrein bound to an inhibitor (inactive kallikrein). It is suggested that the decrease of urinary kallikrein excretion (active and inactive) in the S rats could be a consequence of a genetic defect that may affect the development of hypertension perhaps through the alteration of sodium and water excretion by the kidney.