This study sought to test whether a cognitive-hypnotic intervention could be used to decrease skin reactivity to histamine and whether hypnotizability, physiological variables, attitudes, and mood would influence the size of the skin weals. Thirty eight subjects undertook three individual laboratory sessions; a pretest session to determine sensitivity to histamine, a control session, and an intervention session during which the subject experienced a cognitive-hypnotic procedure involving imagination and visualization. Compared with the control session, most subjects (32 of 38) decreased the size of their weals measured during the intervention session, and the differences between the weal sizes produced in the two sessions were highly significant (N = 38; t = 4.90; p < .0001). Mood and physiological variables but not hypnotizability scores proved to be effective in explaining the skin test variance and in predicting weal size change. Feelings of irritability and tension and higher blood pressure readings were associated with less change in weal size (i.e., a continuation of reactivity similar to that found in the control session without the cognitive-hypnotic intervention), and peacefulness and a lower blood pressure were associated with less skin reactivity during the intervention. This study has shown highly significant results in reducing skin sensitivity to histamine using a cognitive-hypnotic technique, which indicates some promise for extending this work into the clinical area.