After applying topically a cream (0.1 ml) containing corticosteroid (clobetasol propionate), on rat back skin, we examined the morphological alterations of blood vessels, substance P-containing nerve fibers, and cutaneous mast cells. After 3, 6, 10, 15, 30, and 60 min and 4 h, the skin treated was cut out with a sharp knife after killing the animals. The skin pieces were processed into conventional histological sections cut vertically and examined by staining immunohistochemically with anti-substance P serum, by staining with toluidine blue for mast cell granules, and by estimating morphometrically the average areas of vascular cavity and the number of substance P fibers in the dermis. In the dermis and subcutaneous tissue of untreated skin, we found many immunoreactive SP-containing nerve fibers and mast cells in close association. Three to ten min after the treatment, the average area of the vascular cavities steadily increased, and SP-positive fibers became less frequent in the dermis. In concomitant with those events, cutaneous mast cells discharged their granules. Thereafter, the average area of vascular cavities gradually decreased to a minimum at 4 h after the treatment. In contrast, both SP-containing fibers and mast cells reestablished their initial states after the same duration.