Nine patients with adult-onset urticaria pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients.