The pathophysiology of chronic rejection of renal allografts is poorly understood and specific morphologic markers are being sought for its diagnosis. Ultrastructural splitting and reduplication of the basal lamina of the intertubular capillaries (ITCs) have been shown to be consistently associated with transplant glomerulopathy (TG) in renal allografts and have been used as a marker of chronic allograft rejection. Although the presence of ITC abnormalities is extremely helpful diagnostically and has been considered a surrogate for the diagnosis of TG when glomeruli are not available for examination, their specificity has not been tested. This study examined 135 biopsy specimens from renal allografts and native kidneys and categorized the ITC basal lamina alterations into 5 patterns. The results showed that although marked ITC basal lamina abnormalities are characteristically seen in association with TG, lesser degrees of these changes may also be found in native kidneys and in transplants with other types of glomerulopathies. In native kidneys, splitting and reduplication of the ITC basal lamina were observed in cases of active lupus nephritis, membranoproliferative glomerulonephritis type I, crescentic glomerulonephritis, cryoglobulinemia, and hypertension. In allografts, ITC changes were seen in postinfectious proliferative glomerulonephritis, acute cyclosporin toxicity, and hemolytic uremic syndrome, in addition to cases with TG. The histopathologic diagnosis in renal diseases relies heavily on clinical, immunofluorescence, and ultrastructural findings. Therefore, in the transplantation setting, with other less common pathological processes ruled out, the presence of abnormalities of the ITC basal lamina is highly indicative of TG. This association is particularly true for cases with severe ITC abnormalities.