Topical corticosteroids are utilized in the treatment of a wide variety of skin diseases, primarily those involving an inflammatory component. Recent investigations have revealed that one of the effects of long-term usage of steroids is the depletion of skin mast cells. This led to the treatment of patients with urticaria pigmentosa with topical high potency corticosteroids for 6 weeks. At the end of treatment there was a marked reduction in tissue histamine and an absence of mast cells as well as a disappearance of pruritus and Darier's sign. Treated areas remained clinically improved for at least 9-12 months. Observations that corticosteroids profoundly affect mast cells in vivo provides a rationale to devise new treatment regimens for mast-cell-related diseases.