To evaluate the skin reactivity and the mast cell releasibility in the acquired immunodeficiency syndrome (AIDS), 24 patients with AIDS were skin tested with histamine (1 mg/ml) and codeine phosphate (0.9, 0.09, and 0.009 mg/ml), a mast cell degranulating agent. They were compared to 12 HIV-negative healthy volunteers and 16 urticaria-prone subjects. Reactivity to codeine phosphate was lower in patients with AIDS than in HIV-negative subjects. This difference in skin reactivity was the more significant when the AIDS group was compared to the urticaria-prone group. There was no correlation between the reactivity to codeine and the IgE levels. Possible explanations to the decreased skin reacting to codeine in patients with AIDS include a decrease of local mast cell density or releasibility. This suggests that a mechanism related to urticaria and involving mast cells is quite unlikely to be at the origin of the hypersensitivity reactions observed in AIDS.