In six patients with urticaria pigmentosa, population density and ultrastructure of the cutaneous mast cells and histamine levels of the lesional skin were studied before, immediately after, and again 5-8 months after photochemotherapy (PUVA). Immediately after PUVA, the total mast cell number was not reduced, but on separate analysis of the intradermal distribution, significantly fewer mast cells were found in the papillary dermis and correspondingly more mast cells in the adjacent upper dermis. On electron microscopic examination, 4% of the mast cell granules were immature before and 27% after PUVA therapy, based on the lower electron density of the granular matrix. This was associated with a markedly lower histamine content of the lesional skin. Five to eight months after recovery from PUVA, the morphologic changes and the histamine levels had all returned to the pre-PUVA status. These findings were paralleled by a reversal of all clinical beneficial effects that had been observed with PUVA.