We developed a series of methodology to analyze function-structure relationship at single nephron level in animal models of chronic renal disease. Micropuncture measurements were repeated to measure single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) in the same nephrons, and subsequently examine the morphology of these glomeruli by serial section histological analysis. Using this approach, a potential causal link between early functional pattern and late structural abnormalities was examined in glomeruli of 10 Munich-Wistar rats up to six weeks after surgical removal of 5/6 total renal mass. After two weeks all SNGFR and PGC values increased uniformly but to varying degrees within each remnant kidney. Thereafter, values for SNGFR were highly variable, many declining while other increased in the same kidney. PGC showed an initial increase with subsequent decrease by four to six weeks. Serial section histological analysis of these same glomeruli revealed that the extent of glomerular sclerosis positively correlated with the functional deterioration, that is, the degree of reduction in SNGFR (P less than 0.01). However, the degree of sclerosis had no tendency to correlate with the levels of SNGFR or PGC recorded in early stage. These studies indicate that pathophysiologic mechanisms other than, or in addition to, early hyperfunction are involved in determining the extent of glomerular structural damage in this model of chronic renal failure.