The Basenji greyhound (BG) has been proposed as a model of atopic disease because of its chronic relapsing atopic dermatitis as well as airway hyperresponsiveness. We attempted to characterize this model further by comparing its skin wheal-and-flare responses to morphine sulfate and histamine with those of control, nonatopic mongrel dogs. We found that BG dogs had significantly smaller skin responses than did the control dogs to all but two concentrations of histamine used. In contrast, BG dogs demonstrated greater skin response to morphine at the three lowest concentrations used but had a significantly smaller skin response at the highest dose of morphine. Skin punch biopsy specimens revealed decreases in histamine content after morphine exposure but no difference in histamine content of the unexposed skin or of morphine-exposed skin for the two groups of dogs. When percent histamine release was compared, however, BG dogs were found to release a significantly greater proportion of histamine in response to morphine than control dogs. Although there was no significant difference in total mast cell counts for the two groups, the BG dogs had significantly fewer formalin-insensitive mast cells in unexposed skin than control dogs. We conclude that skin responses in BG dogs are characterized by decreased end organ responsiveness and greater releasability of mast cells in response to nonimmunologic stimulation.