A newborn foal developed generalized cutaneous mastocytosis characterized by multiple elevated nodules of mast cells in skin and basophil hyperplasia in bone marrow. Skin lesions began as small aggregates of mast cells that progressively enlarged, ulcerated, and regressed spontaneously. Eosinophil infiltration, collagen necrosis, and fibroplasia were characteristic of advanced lesions. Many new lesions developed during the first month of life but numbers progressively diminished. Large numbers of mast cells were present in biopsies of lymph node, spleen and bone marrow. Discrete aggregates of mast cells were present in the bone marrow postmortem but no other significant change was seen. Mast cells contained large amounts of histamine but little serotonin. Ultrastructurally, their cytoplasmic granules were chiefly granular with few dense forms. In cell culture, mast cells from early lesions maintained mitotic activity through 14 passages. Cells obtained from older lesions were rapidly overgrown with fibroblasts. An equine herpesvirus isolated from cultures of cutaneous mast cell lesions and of spleen was not thought to be related to the disease.