Mast cell proliferative disorders include urticaria pigmentosa, localized to the skin, and systemic mastocytosis, with progression from urticaria pigmentosa to systemic mastocytosis in some adults. We have evaluated the presence of basophil/mast cell precursors in urticaria pigmentosa and systemic mastocytosis using an in vitro assay for cells which form histamine-positive peripheral blood granulocyte colonies in methylcellulose. In 17 cultures from 10 patients with mast cell proliferative disorders (6 urticaria pigmentosa, 4 systemic mastocytosis), the frequency of histamine-positive granulocyte colonies was significantly higher in systemic mastocytosis (40% colonies picked) than in urticaria pigmentosa (15%, p less than 0.002). The mean histamine content per cell of urticaria pigmentosa patient colonies was less than or equal to 0.1 pg compared to 0.7 +/- 0.1 pg in systemic mastocytosis patient colonies. Precursor assays done serially at different times in individual patients appeared to reflect clinical extent of disease. In one patient with urticaria pigmentosa, a repeatedly normal number of histamine-positive colonies paralleled no change in clinical course, while in 2 others (1 systemic mastocytosis, 1 urticaria pigmentosa) increasing skin lesions, leukopenia, increased urinary histamine or refractoriness to therapy was accompanied by an increase in the frequency of basophil/mast cell precursors. Using an index of disease activity, the frequency of histamine-positive colonies was significantly higher in active, versus inactive, mast cell proliferative disorders (p less than 0.0001). These studies confirm the biologic relevance of mast cell proliferation in mast cell proliferative disorders, and suggest that precursor assays using histamine content of granulocyte colonies may be useful in predicting extent of disease.