Focal segmental glomerulosclerosis evolves toward chronic renal failure (CRF) with a highly variable rate; in particular, a group of patients with a much more rapid decline of renal function has been described. The purpose of this study was to evaluate the usefulness of morphometry in identifying those cases with a faster decline in renal function. Two groups of patients have been studied: six with rapid evolution toward CRF (group 1) and six without reduction in renal function during a follow-up of up to 10 years (group 2). The results of the morphometric analysis of glomeruli were as follows: mean glomerular area: 30,550 +/- 5,259 microns2 (group 1) versus 22,667 +/- 5,078 microns2 (group 2) (P = 0.01); maximum glomerular area: 40,827 +/- 9,508 microns2 (group 1) versus 30,445 +/- 7,224 microns2 (group 2) (P = 0.02); mean glomerular diameter: 193.9 +/- 15.8 microns (group 1) versus 161.8 +/- 16.8 microns (group 2) (P = 0.003); and caliper diameter: 328.6 +/- 20.6 microns (group 1) versus 260.6 +/- 36 microns (group 2) (P = 0.001). Values of body surface area were not different between the two groups (1.85 +/- 0.34 m2 v 1.6 +/- 0.13 m2) (P = NS). Our results suggest that glomerular hypertrophy in the course of focal segmental glomerulosclerosis is correlated with a faster decline toward CRF. It might represent a compensatory hypertrophy that would immediately precede a rapid decline in renal function or it might be the expression of the preexisting condition (meganephronia), which predisposes to the development of CRF.