We studied the contributions of glomerular hypertrophy in renal disease. The patients were 20 cases of IgA nephropathy with prolonged proteinuria, 13 cases of Alport syndrome and 12 cases of focal glomerular sclerosis (FGS). All patients had a normal creatinine level on renal biopsy. We determined the mean glomerular tuft area in the equatorial region of five glomeruli that showed no sclerotic change in each patient using an image analyzer and compared the value with the mean value in normal controls. Glomerular hypertrophy was defined as a value over the mean glomerular tuft area +1SD of normal controls. Glomerular hypertrophy was found in 14 IgA nephropathy cases (70.0%), 4 Alport syndrome cases (30.7%) and 8 FGS cases (66.7%). The incidence of glomerular hypertrophy was significantly higher in IgA nephropathy than in Alport syndrome and FGS showed a higher tendency compared with Alport syndrome. Of the patients with renal insufficiency, 4 of 6 IgA nephropathy cases (66.6%), 0 of 5 Alport syndrome cases (0%) and 1 of 3 FGS cases (33.3%) showed glomerular hypertrophy, IgA nephropathy patients showed the highest incidence of glomerular hypertrophy. The interval between the final biopsy and renal insufficiency showed no significant difference in this study. In IgA nephropathy, obsolescent glomeruli were significantly increased in the group in which the glomerular tuft area was over the mean +2SD compared with the group with an area less than the mean +2SD. FGS cases showed no relationship between the ratio of obsolescent glomeruli to whole glomeruli and glomerular hypertrophy. This study suggested that glomerular hypertrophy may cause declining renal function in IgA nephropathy, but not in Alport syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)