The relation between urinary kallikrein excretion ( Ukal ) and rejection, graft function, and blood pressure was studied in 45 renal transplant recipients. Ukal was assayed by means of an enzymatic (amidolytic) method, as well as with a specific radioimmunoassay. In a group of 10 patients studied longitudinally from the day of transplantation till day 35 +/- 3, an increase in urinary amidolytic activity without a concomitant increase in kallikrein antigen excretion was found to precede 11 out of 14 rejection episodes. This increased amidolytic activity generally persisted for several days. It was demonstrated by chromatography using an immunoadsorbent column of antiurokallikrein that the rejection-associated esterase, or esterases, differed from urokallikrein . In 35 outpatient recipients with stable graft function, Ukal excretion was decreased compared with that of healthy controls (42 +/- 7.5 vs. 107.5 +/- 7.3 micrograms/24 hr by radioimmunoassay and 0.70 +/- 0.08 vs. 1.10 +/- 0.07 U/24 hr, using the amidolytic method); for these patients a significant correlation between Ukal excretion and creatinine clearance was found (P less than 0.02). Both in transplant recipients and in controls there was a close correlation between the results of the two Ukal assays (P less than 0.001). No significant relation between Ukal excretion and blood pressure was found, either for patients or for controls. It is concluded that acute graft rejection is accompanied by an increased excretion of nonurokallikrein esterase(s). The lower Ukal excretion in patients with stable renal function seems to be related to their reduced renal function. No relation between Ukal excretion and blood pressure levels was found.