It is not clear whether glomerular hypertrophy is related to the pathogenesis of focal segmental glomerulosclerosis (FSGS). We analyzed renal biopsies from 20 adults with FSGS by morphometry, and the data were compared with those from age- and sex-matched patients with minimal lesion. Mean glomerular volume in the FSGS group was significantly larger than that in the minimal lesion group[(3.4 + 1.1 vs 2.5 0.5)x10(6) micrometer3, P<0.01]. The percentage of glomeruli with global and segmental sclerosis in FSGS group was significantly correlated with the mean glomerular volume (r=+0.66, P<0.001). Relative interstitial volume of renal cortex in the FSGS group was correlated with the serum creatinine concentration(r=+0.5, P<0.05). These results suggest that glomerular hypertrophy observed in our patients with FSGS was related to nephron loss caused by glomerulosclerosis. The interstitial fibrosis may lead to obliteration of postglomerular interstitial capillary network with secondary elevation of glomerular capillary pressure resulting in progressive loss of renal function.