This study was designed to directly examine the role of mast cells and the histologic changes in the late phase (4-48 h) of hematoporphyrin derivative-induced phototoxicity. BALB/c mice were rendered phototoxic by intraperitoneal injection of HpD, followed by exposure to 1.59 kJ/m2 of 396-406 nm radiation. Immediately before radiation, and at 4, 8, 12, 18, 24 and 48 h after radiation, the ear thickness, serum histamine levels and histologic changes of ears were examined. A maximal net increase in ear thickness of 33.5 +/- 0.3 X 10(-2) mm (mean +/- SE) was noted at 12 h, associated with a maximal net increase of serum histamine (43.3 +/- 11.6 ng/ml, mean +/- SE), and a maximal mast cell degranulation. Other histologic changes consisted of mild epidermal spongiosis at 18-24 h, and a predominant neutrophilic infiltrate, which peaked at 24 h (211.6 +/- 0.4 cells/mm2). No significant alteration was observed in control mice. These data indicated that mast cells participate in the late phase of HpD-induced phototoxicity in mice.