It has been proposed that interstitial fibrosis is causally related to a progressive decrease in glomerular filtration rate (GFR), in patients with various renal diseases. We examined the relationship between morphological and functional parameters in 200 samples from 74 patients with mesangial proliferative glomerulonephritis. The glomerular lesion was semiquantitatively analyzed using the Glomerular Index (GI). Interstitial volume (IV) was determined by the point-counting method. Both GI and IV showed a significant negative correlation with Ccr and a positive correlation with serum creatinine. The serial change in IV from the first to the last biopsy (delta IV) showed a weak but significant negative correlation with those in Ccr, over the same period (delta Ccr). The serial change in GI (delta GI) did not correlate with delta Ccr. There was a significant positive correlation between GI and IV and between delta GI and delta IV. These data confirmed a cause-and-effect relationship between interstitial damage and GFR and also showed that the glomerular lesion as well as the interstitial change play an important role in the deterioration of renal function. Thus, the interstitial lesion alone should not be emphasized as a determinant of renal function, as we noted a close correlation between the interstitial and glomerular lesion. Interstitial damage is apparently secondary to the glomerular lesion in patients with mesangial proliferative glomerulonephritis.