Studies have suggested that glomerular size increases in childhood minimal lesion with age or growth. To examine whether mean glomerular volume (MGV) of pediatric patients with focal segmental glomerulosclerosis (FSGS) also increases with age and whether FSGS by itself can contribute to glomerular hypertrophy, we studied 67 children (40 boys, 27 girls) with primary FSGS and 95 children (68 boys, 27 girls) with minimal lesion by morphometry. FSGS patients had segmental sclerosis affecting 17.1% +/- 14.8% of the glomeruli. The percentage of segmental glomerulosclerosis was not related to age. MGV increased with age in the FSGS patients (r2 = 0.36, P < 0.001) and in the minimal lesion patients (r2 = 0.37, P < 0.001). MGV of children with FSGS is significantly larger than that of the minimal lesion group [(14.8 +/- 5.7) x 10(5) microm3 vs. (12.1 +/- 3.7) x 10(5) microm3, P < 0.001]. Multiple regression estimates suggest that the FSGS lesion affects MGV independently (P < 0.001). The volume density of mesangium and the volume density of cortical interstitium were significantly greater in the FSGS patients than in the minimal lesion patients (P < 0.001). These results indicate that MGV of pediatric FSGS patients increases with age and that the FSGS lesion itself may cause glomerular hypertrophy, possibly via mesangial expansion. Thus, glomerular hypertrophy in childhood minimal lesion may be an indicator of FSGS that is undetected because of the problem of sampling.