In human kidney transplantation the main cause of declining long-term graft function is chronic allograft nephropathy (CAN). Recent studies have implicated human mast cells (MC) in chronic inflammation and fibrosis, MC can be subtyped according to protease content: MC(T) containing tryptase only and MC(TC) containing both tryptase and chymase. We investigated immunohistochemically whether numbers and subtypes of MC in biopsy specimens 100 d after transplantation could predict subsequent fibrosis and graft dysfunction. The total number of MC/high-power field at 100 d after transplantation correlated significantly with change in creatinine clearance (DeltaCcr), defined as (Ccr at 100 d) - (Ccr at 3 yr) (R = 0.597, p = 0.0021); fibrosis index (FI) at 100 d (R = 0.583, p = 0.0066); and DeltaFI, defined as (FI at 3 yr) - (FI at 100 d) (R = 0.406, p < 0.05). The ratio of MC(TC) to total MC at 100 d also correlated with DeltaCcr (R = 0.491, p = 0.0148), FI at 100 d (R = 0.527, p = 0.0081), and DeltaFI (R = 0.417, p < 0.05). Thus, increases in number of total MC and the ratio of MC(TC) to total MC in early biopsy specimens were related to decline of long-term graft function and fibrosis.