This study evaluated mast cells in tissue around loose total hip implants. Interface and pseudocapsular tissues were obtained from 6 patients with a loose hip prosthesis. Mast cells were labeled with monoclonal mouse antihuman antibodies against tryptase and chymase in avidin-biotin-peroxidase complex staining and were quantitated morphometrically by means of a semiautomatic Kontron image analyzer. Almost all mast cells in situ were chymase-positive and tryptase-positive connective tissue cells. The mean number of such cells per mm2 of tissue increased in this rank order: interface (9.98 +/- 5.03 cells) < pseudocapsule (15.85 +/- 4.99 cells) < control knee synovium (25.08 +/- 8.64 cells). Mast cells in periprosthetic tissue, in contrast to normal knee synovial tissue, exhibited granule release. Mast cells around loose hip prostheses appeared to be activated by connective tissue mast cells. These were found in diminished numbers and in a degranulated state in the interface tissue between implant and bone. Mast cell activation in loco may thus lead to significant local production and/or release of proinflammatory mast cell mediators. Prevention of mast cell activation (degranulation) could prove useful in the postponement of loosening of the totally replaced hip.