To investigate the physiologic role of plasma inactive renin and its relationship to plasma kallikrein, we measured the changes in plasma active renin, inactive renin and prekallikrein levels in 14 uremic patients before and after hemodialysis. Blood was collected before, during and after hemodialysis, and prior to the next dialysis session. Plasma active renin was measured by radioimmunoassay of generated angiotensin I after addition of an exogenous substrate. Plasma inactive renin was activated by trypsin. Plasma prekallikrein was measured by the kallikrein-like activity on synthetic substrate S-2302 after activation of prekallikrein. The results showed that there was no change in blood pressure before, during or after dialysis, whereas the change in body weight after dialysis was significant. There was also no significant difference in the plasma active renin, inactive renin and prekallikrein levels for any of the collection periods. Plasma active renin was significantly correlated with inactive renin. The correlation between the active renin/total renin ratio and the plasma prekallikrein level was also not significant. These results suggest that in uremic patients undergoing chronic hemodialysis, the response of the renin system to acute plasma volume change is blunted. These data only provide evidence that plasma active renin is linked with inactive renin, but provide no evidence to support the idea that plasma inactive renin is a precursor of active renin or that plasma kallikrein is related to activation of inactive renin in vivo.