Morphometric studies were performed in 15 patients with chronic renal allograft rejection. Biopsy cores were serially sectioned so that atubular glomeruli could be identified and volumes of individual glomeruli could be measured. Control tissue was obtained from 9 cadaver donors and 8 living donors. Serial sectioning revealed that atubular glomeruli were as common as sclerotic glomeruli in chronic rejection. The prevalence of atubular glomeruli averaged 18 +/- 15% (mean +/- SD) in recipients with chronic rejection, 2 +/- 2% in cadaver donors, and 1 +/- 3% in living donors (P<0.05, recipients vs. donor groups). In comparison, the prevalence of sclerotic glomeruli averaged 19 +/- 13%, 4 +/- 7%, and 7 +/- 10% in the three groups (P<0.05 recipients vs. donor groups). Atubular glomeruli exhibited reduced mean volume (3.1 +/- 0.9 x 10(6)micron(3) vs. 4.5 +/- 1.5 x lO(6)micron(3), atubular vs. open glomeruli in recipients, P < 0.05) but could not be distinguished from open glomeruli by their appearance on single sections. Recipients with chronic rejection exhibited tubular atrophy and interstitial fibrosis with an increase in the interstitial volume fraction to 51 +/- 14% as compared with 29 +/- 6% in cadaver donors and 17 +/- 2% in living donors (P<0.05 recipients vs. donor groups). Similar interstitial expansion was observed in recipients with a high prevalence of atubular glomeruli, recipients with a high prevalence of sclerotic glomeruli, and also in four recipients in whom the predominant form of glomerular injury was transplant glomerulopathy. These results suggest that mechanisms responsible for development of atubular glomeruli are among the processes that contribute to loss of graft function in patients with chronic rejection.