Selective markers for human mast cells are of paramount importance for understanding their role in physiological and pathological processes. A mouse monoclonal antibody (MAb) designated 2C7, raised against in vitro-derived human mast cells, was used in immunoenzymatic analysis of sections from a variety of human organs. Double immuno-labeling with 2C7 and tryptase, chymase, Fc∊RIα, and c-kit was performed on cryostat tissue sections from skin, colon, uterus, breast, stomach, bladder, and lung. MAb 2C7 stained greater than 93% of the tryptase+ or chymase+ mast cells in all tissues examined. In addition, the majority of cells stained with the tryptase or chymase also stained for Fc∊RIα. However, there were a significant number of Fc∊RIα+ cells in all tissues studied that were tryptase− and/or chymase−. In contrast, MAb 2C7 in double immunoenzymatic staining co-localized with 93–96% of the Fc∊RIα+ cells in all tissues. Analysis for c-kit expression on the different tissues revealed that the majority of tryptase+ or chymase+ cells in skin, uterus, bladder, and lung stained with c-kit. However, only approximately 70-78% of tryptase+ cells in colon and stomach were c-kit+. These data suggest that MAb 2C7 appears to identify mature mast cells and a population of Fc∊RIα+, chymase−, and tryptase− cells in a variety of human tissues.