Mast cells may be more abundant in the tissues of uremic patients and may contribute to itching via mediator release. Because mast cell (MC) granule release may be inhibited by ultraviolet B (UVB) radiation, we investigated skin MC in the superficial dermis by quantitative histomorphometry before and after whole body UVB for uremic itching. Toluidine blue-stained 3.5 mm punch biopsy specimens were examined with a micrometer grid after separate coding. Upon entry to the study, itching dialysis patients indicated their itching intensity on a visual analog scale (0 to 10). Concurrent study of living, related kidney donors (controls, n = 11) and their recipients (n = 11) showed no differences in MC number per unit area. Compared to controls, skin MC number was not greater in itching dialysis patients (n = 20). MC number decreased after 2 months of UVB from 1.6 +/- 0.6 (standard deviation) to 1.0 +/- 0.7 (n = 11, p = 0.025). Pre-UVB total plasma calcium correlated directly with itching intensity, but not with MC number. Plasma phosphate and intact parathyrin level were not statistically related to itching or MC number. Of the 14 subjects that completed UVB, 8 had objective benefit, and mean itching intensity declined from 7.1/10 to 5.2/10 in the 14 subjects. The conclusion is that although skin MC number may decline with chronic UVB, MC number is not related to uremic itching, and hypercalcemia, but not elevation of parathyrin or plasma phosphate, relates statistically to severe uremic itching.