Hemangiomas, the most common tumors of infancy, are characterized by a postnatal period of rapid growth, followed by a phase of gradual involution. The proliferative phase is characterized by increased numbers of endothelial and mast cells and thickened basement membrane. Ultrastructural analysis of hemangiomas in the late proliferative phase showed that mast cells had numerous fingerlike processes aligned parallel to the outer lamina of the thickened basement membranes surrounding the vessels and to the surfaces of opposing cell membranes. We found evidence of different types of interactions between mast cells and adjacent connective tissue cells (fibroblasts, macrophages, multinucleated giant cells, and plasma cells) in the perivascular regions of the lesions. Intercellular contacts were observed in areas where these mast cell processes were in close association to the opposing cell membrane. Areas of membrane fusions were seen between cell types. Coated vesicles and pinocytotic vesicles were present along the periphery of cells adjacent to mast cells. Occasionally, cytoplasmic bridges were found between mast cells and fibroblasts. These ultrastructural findings suggest the proliferation and involution of hemangiomas are determined by interactions between the various types of cells found in the lesions.