Urinary kallikrein excretion (UKE) was measured in 20 patients before and after hemodialysis (HD). When compared to the values of normal subjects (136 +/- 56 micrograms/24 h, n = 100), UKE was decreased in all patients before HD (6.6 +/- 5.8 micrograms/24 h, p less than 0.001, n = 20). After HD a significant increase in 24-hour UKE was observed in all patients (18.6 +/- 7.2 micrograms/24 h, p less than 0.05, n = 20). Expressed as the individual percent increase, the UKE enhancement ranged from 16 to 670%. It was due to an enhancement in the excretion of the active form which represented 52 +/- 6.8% before HD and reached 76.3 +/- 7.5% of the total form after HD (p less than 0.01). The excretion of the inactive form remained unchanged. The increase in UKE was found to be significantly correlated with reductions in urinary sodium, potassium, and osmolality (r = -0.826, r = -0.568, r = -0.847, respectively, p less than 0.01, n = 20). The increase in UKE following HD could not be explain by an increase in aldosterone as urinary aldosterone decreased. A transient improvement in intracellular homeostasis (removal of inhibitory toxins and normalization of osmotic pressure) could be evoked. The increase in UKE 24 h after HD points out a new situation confirming the relations of UKE with changes in osmolality and extracellular volume.