The time course for functional reinnervation and development of supersensitivity to norepinephrine (NE) in the denervated rat kidney was studied using an in situ kidney preparation perfused at constant flow. Changes in perfusion pressure were measured during renal nerve stimulation (RNS, 1-10 Hz) and after administration of NE (1-50 ng, ia) up to 8 wk after unilateral renal denervation or a sham operation. During the first 2 wk after denervation, supersensitivity to NE was present, but there was no response to RNS. Between 24 and 32 days after denervation, RNS produced responses averaging 40% of control in denervated kidneys and supersensitivity to NE was still present. A fluorescence assay was used to determine that the NE concentration in kidneys 24-32 days after denervation was less than 30% of that found in control kidneys. At 8 wk, average responses to RNS in denervated kidneys were not significantly different from innervated kidneys, while supersensitivity to NE was still present. These results indicate that functional reinnervation of the renal vasculature begins to occur between 14 and 24 days after denervation, and that complete return of function may occur by 8 wk. The response to RNS during reinnervation appears to be due to a combination of regeneration of nerve fibers and denervation supersensitivity to NE.