The nature of class II-positive cells in normal and transplanted human heart has been investigated using immunoperoxidase and dual-immunofluorescent techniques. In normal heart approximately 83% of DR expression can be accounted for by EN4+ endothelial cells, most of which express intercellular adhesion molecule 1 constitutively. Few cells bearing the leukocyte common antigen are found in normal heart; most of them are RFD7+ macrophages or T cells. There is a paucity of RFD1+ dendritic cells. In transplanted heart showing signs of rejection, the infiltrate consists of RFD7+, RFD1+, RFD7+, RFD1+ cells and T lymphocytes. The increased class II expression within these biopsies is confined to the infiltrating cells. Dual-immunofluorescence demonstrates that nearly all the RFD1+ cells are from the recipient. In conclusion, in normal heart presentation of allogeneic class II is by the intercellular adhesion molecule-1-positive endothelial cells. After transplantation, there is an influx of recipient cells of the macrophage/dendritic series which are probably able to process allogeneic class II.