A close association between glomerular hypertrophy and subsequent sclerosis had been demonstrated in diverse animal and human studies. We investigated the relationship between the glomerular volume and glomerular constituents (mesangial matrix, mesangial cells and capillary lumens) in human mesangial proliferative glomerulonephritis (GN). The data were obtained from glomeruli in the specimens of 23 patients undergoing repeat renal biopsies. Glomerular volume and glomerular constituents of each patient were obtained by averaging those of all glomeruli in each specimen. The interval from the first biopsy to the second was 51.2 +/- 6.8 months and the number of glomeruli included in each specimen was 16 +/- 1. Between glomerular volume and fractional mesangial volume, three patterns were recognized. In 8 of 23 patients glomerular volume and fractional mesangial volume were increased in the second biopsy (Group A). In 12 of 23 patients glomerular volume was decreased and fractional mesangial volume increased in the second biopsy (Group B), and in 3 of 23 patients glomerular volume was increased and fractional mesangial volume decreased in the second biopsy (Group C). One patient who underwent renal biopsy three times shifted from Group A to Group B in the course of mesangial proliferative GN. At the final follow-up, 4 of 12 patients in Group B required hemodialysis in contrast to none of 8 patients in Group A. Between glomerular volume and fractional mesangial volume, a positive and inverse relation existed, and we considered that in the course of mesangial proliferative GN, initially, glomerular size increases and thereafter decreases progressively. With glomerular enlargement, mesangial matrix expansion, glomerular capillary enlargement and relative decrease of the number of capillary lumen profiles and mesangial cells per glomerulus to increased glomerular volume were recognized. We concluded that these histological changes play a role in the progression of mesangial proliferative GN in humans as has been speculated in animal models of renal ablation.