The rate of tissue kallikrein (EC 3.4.21.35) excretion into the urine has been examined with an active site-specific radioimmunoassay for kallikrein in renal transplant recipients, in post-uninephrectomy kidney donors, and in a normal control population. Normal individuals on uncontrolled diets excreted 96.88 +/- 7.00 (SEM) micrograms of active kallikrein/24 hr and 113.68 +/- 8.39 micrograms of total kallikrein/24 hr, as determined after trypsin treatment of urine samples. Uninephrectomized donors secreted significantly less (P less than 0.05) active (44.99 +/- 6.39 micrograms/24 hr) and total (73.59 +/- 11.95 micrograms/24 hr) kallikrein than either the entire normal population or an age-matched subpopulation. Recipients with good renal function who had received kidneys 2 to 13 years prior to kallikrein assay excreted less (P less than 0.05) active (13.21 +/- 2.50 micrograms/24 hr) and total (18.69 +/- 3.65 micrograms/24 hr) kallikrein than either normal or uninephrectomized populations. Similar values for active (11.05 +/- 1.56 micrograms/24 hr) and total (17.60 +/- 1.96 micrograms/24 hr) kallikrein were seen in patients who had received kidneys within 6 months of assay. Thus, kallikrein excretion in kidney recipients remains significantly lower than in uninephrectomized donors. As compared to normal individuals, the reduced kallikrein excretion in post-uninephrectomized kidney donors and in renal allograft recipients suggests that renal kallikrein excretion may reflect functional distal tubular mass.