To determine whether there is glandular kallikrein in plasma, untreated as well as acetone-treated and heated-acidified rat plasmas together with rabbit anti-rat urinary kallikrein were used in counterimmunoelectrophoresis. Precipitation bands were observed with untreated and acetone-treated plasma, suggesting that glandular kallikrein is present in plasma. This enzyme, however, cannot be quantified in the untreated plasma by a new direct RIA since kallikrein inhibitors present in plasma appear to interfere with this assay. Destroying the inhibitors by acetone treatment or by heat and acidification of the plasma partially solves this problem. In the second part of the study, this RIA as well as a kininogenase and an esterase assay were used to measure urinary kallikrein in DOCA-salt treated rats and in control rats. There is a significant correlation between urinary kallikrein measured by the direct RIA and by a kininogenase method (r = 0.75, p less than 0.001) in both DOCA-salt treated and in the control rats. Although the results obtained by the direct RIA and an esterase method significantly correlate in the control rats (r = -0.048, p greater than 0.1). This suggests that part of the urinary esterase activity in the Doca-salt rats is due to urinary enzymes other than kallikrein and that the esterase assay is not reliable for the determination of urinary kallikrein in pathological situations. However, the direct RIA and the kininogenase assay are suitable for this purpose.