The alpha-smooth muscle (alpha-SM) actin isoform is expressed normally by vascular SM cells and by stromal fibroblastic cells in pathological conditions leading to fibrosis. In order to investigate the relation between kidney fibrosis and alpha-SM actin expression, we studied 51 renal biopsies from 45 patients: 30 with various forms of glomerulonephritis; 1 with acute tubular necrosis; 1 with acute interstitial nephritis, and 13 renal transplant recipients. The presence of alpha-SM actin was examined by using anti-alpha SM-1, a mouse monoclonal antibody (IgG2 alpha) specific for alpha-SM actin. alpha-SM actin scores were estimated semiquantitatively, as were glomerulosclerosis and interstitial fibrosis. In acute tubular necrosis and in well-functioning grafts, alpha-SM actin expression was limited to vascular SM cells. In glomerular diseases, alpha-SM actin expression was upregulated in mesangial area in 25 of 36 biopsies, and even more frequently in the periglomerular and peritubular interstitium (34 of 36 cases, chi 2= 7.6, P< 0.01). Whereas glomerular alpha-SM actin expression seemed to decrease as glomerulosclerosis progressed, there was a positive correlation between interstitial alpha-SM actin scores and the degree of interstitial fibrosis. Similarly, interstitial alpha-SM actin expression was found in acutely or chronically rejected kidneys, but not in well-functioning grafts. We conclude that upregulation of alpha-SM actin in the glomerulus indicates mesangial cell activation and is not always correlated with the degree of glomerulosclerosis. In contrast, interstitial upregulation of alpha-SM actin which indicates myofibroblast activation is correlated with the degree of interstitial fibrosis.