To asses the efficacy of ketotifen (Zaditen; Sandoz Pharmaceuticals, Basel, Switzerland) for the treatment of pediatric mastocytosis, eight children who exhibited symptoms as a result of mastocytosis were enrolled in a 12-week, double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine (Atarax; Roerig, New York, N.Y.). Efficacy of each drug was assessed by daily symptom scores and plasma- and 24-hour urine-histamine levels. After completion of the study, symptom scores revealed that seven of the eight children exhibited a greater reduction in symptoms while they were receiving hydroxyzine (p less than 0.05). The symptoms most likely to improve with treatment with hydroxyzine were flushing and abdominal pain. Analysis of plasma- and 24-hour urine-histamine levels at the beginning and end of each trial period of each drug revealed no significant differences (p greater than 0.20). Changes in 24-hour urine-histamine levels, but not plasma-histamine levels, correlated with changes in symptom scores. We conclude that ketotifen offers no advantage over hydroxyzine in the treatment of pediatric mastocytosis.