In most forms of renal injury, even those due to a primary glomerular process, the extent of tubulointerstitial scarring is a critical determinant of renal functional reserve and prognosis. Yet, little is known about the functional characteristics of the interstitial cells that mediate the processes of chronic tubulointerstitial injury. In this study, tissues from normal kidney (N = 7), from nephrectomies removed for allograft rejection (N = 14) and chronic pyelonephritis (N = 2), and from a cohort of 128 biopsies exhibiting a range of glomerulopathies and tubulointerstitial injury were characterized with antibodies to mesenchymal cells (alpha-smooth muscle actin, desmin) by immunohistology. Selected normal kidneys were also studied by immunoelectron microscopy. Normal adult kidneys contain a widespread population of cortical interstitial cells that constitutively express alpha-smooth muscle actin but not desmin. Immunoelectron microscopy shows that these cells are fibroblasts and not capillary endothelial cells or leukocytes. It has previously been shown that these cells constitutively express platelet-derived growth factor receptor beta and the p75 nerve growth factor receptor. Accumulations of cells expressing smooth muscle actin were identified at sites of chronic tubulointerstitial injury in allograft and pyelonephritic kidneys. The cohort of 128 renal biopsies also revealed accumulations of muscle actin-expressing cells at sites of interstitial injury. These findings demonstrate that a population of interstitial cells with some muscle-like features can be identified in normal kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)