We have made a blind retrospective analysis of 334 renal biopsies, each containing more than 10 glomeruli, from adults and children with glomerulonephritis, in order to assess the clinicopathological significance of segmental lesions. These were defined as endocapillary proliferation and/or sclerosis involving capillary loops, and a less than half the glomerular tufts. On optical microscopy of paraffin-embedded material, 57 biopsies containing segmental lesions were independently classified by two observes as "focal proliferative glomerulonephritis" or "focal segmental glomerulosclerosis". These results were then reviewed with immunofluorescence, electron microscopic and clinical data and an "executive" diagnosis reached. Scarred focal proliferative glomerulonephritis could not be reliably distinguished from focal segmental glomerulosclerosis by optical microscopy alone. Some cases of focal proliferative glomerulonephritis are not associated with systemic disease and may have negative immunofluorescence findings, and we were unable to distinguish scarring in these patients from the lesion of focal segmental glomerulosclerosis with any of the tools at our disposal. Some patients with scarred focal proliferative glomerulonephritis showed profuse proteinuria, a nephrotic syndrome and progression to renal insufficiency. These cases cannot therefore be differentiated from focal segmental glomerulosclerosis by their clinical features. It would seem that the morphological lesion of focal segmental glomerulosclerosis should be regarded as focal segmental glomerular scarring from a variety of insults, rather than a distinct disease entity.