Rat peritoneal mast cells purified on a Percoll gradient were activated by substance P (SP) and the effect of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet light (UVA) irradiation (8-MOP/UVA) on SP-induced histamine release from the cells was investigated. At a concentration of 10(-5) M SP caused a significant histamine release. 8-MOP or UVA irradiation alone at the doses used in the present study neither induced a histamine release nor had any significant effects on SP-induced histamine release from mast cells. On the other hand, 8-MOP/UVA inhibited SP-induced histamine release; this inhibition was dependent on the UVA doses (0.5-3.0 J/cm2) and was accompanied by a reduction in the rise in intracellular calcium concentrations ([Ca2+]i). These data suggest that 8-MOP/UVA inhibits histamine release from SP-activated rat peritoneal mast cells by suppressing the rise in [Ca2+]i.