Renal tubular reabsorption of L-histidine (His) was measured in vivo et situ by continuous microperfusion and free flow micropuncture of single proximal convoluted tubules of the rat kidney. The reabsorption is shown to be saturable. A permeability coefficient (P) of less than 29 microns 2 . s-1, a maximum reabsorption rate (J max) of 2.75 +/- 1.05 greater than J max greater than 1.97 +/- 0.86 (SEM) nmol . m-1 . s-1 and an affinity constant (Km) of 13.8 +/- 4.2 greater than Km greater than 10.9 +/- 4.0 (SEM) mol . 1-1 (lower values for P = 29 microns 2 . s-1, higher values for P = 0) were calculated from the microperfusion data. Using these constants and taking backflux of His and water reabsorption into account a good fit with the concentration profile of His along the proximal tubule--measured by free flow micropuncture--was obtained. Varying the buffered pH-values of the perfusion fluids (5.0 or 7.4) influenced neither the active reabsorption nor passive permeability of His. This indicates that the charge of the imidazol group of His does not play a significant role in His reabsorption. Further experiments showed that the addition of 20 mmol . 1-1 L-arginine--a strong inhibitor of the reabsorption system for dibasic amino acids--did not have a significant effect on the reabsorption of L-histidine. It is concluded, therefore, that His is reabsorbed by a system for neutral amino acids. Non ionic diffusion does not play an important role for His reabsorption.