Biochemical heterogeneity of arginine metabolism along kidney proximal tubules. By using an in vitro single tubule micromethod of high specificity, in four different species of mammals it has been observed that (a) arginine synthesis from citrulline (arginine synthase activity, E.C. 6.3.4.5 and E.C. 4.3.2.1) is restricted to the early portions of proximal convoluted tubules, whereas (b) urea production from arginine (arginase activity, E.C. 3.5.3.1.) is present mainly in the cortical (CPST) and even more in the outer medullary (OSPST) portions of straight proximal tubules. The data suggest that (a) in early PCT cells, the citrulline reabsorbed from glomerular filtrate is converted into arginine, which in turn crosses peritubular cell membranes together with reabsorbed arginine, and (b) the urea formed in CPST and OSPST cells might passively diffuse into the luminal fluid entering Henle's loops. Such urea secretion might contribute to sustain the process of urea recycling in kidney medulla and thereby participate in the mechanism of urine concentration.