Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis, Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8 +/- 1.6 cells/mm(2) in minimal change nephrotic syndrome (n = 7), 1.5 +/- 0.7 cells/mm(2) in minor glomerular abnormalities without nephrotic syndrome (n = 7), 6.5 +/- 7.7 cells/mm(2) in membranous nephropathy (n = 10), 12.9 +/- 15.5 cells/mm(2) in lupus nephritis (n = 15), 13.4 +/- 8.3 cells/mm(2) in focal segmental glomerular sclerosis (n = 6), 18.5 +/- 21.1 cells/mm(2) in ANCA-related nephropathy (n = 5), 19.8 +/- 14.2 cells/mm(2) in membranoproliferative glomerulonephritis (n = 5), 21.3 +/- 17.7 cells/mm(2) in immunoglobulin A (IgA) nephropathy (n = 42), and 33.0 +/- 33.8 cells/mm(2) in diabetic nephropathy (n = 10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r = 0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r = 0.72; P < 0.0001) and fibrosis (r = 0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury. (C) 1998 by the National Kidney Foundation, Inc.