Leukocyte chemotaxis was studied in 11 patients with severe childhood onset atopic dermatitis at a time when their disease was relatively quiescent. Pyoderma had been an important complication of the dermatitis in these patients. The chemotactic responsiveness of patient neutrophils and monocytes was on the average not significantly different from that of healthy control subjects, although three patients were identified who had significantly impaired responses. No correlation between IgE levels and leukocyte chemotaxis was observed. Because excessive amounts of histamine have been recovered from the skin of patients with atopic dermatitis, we evaluated the effects of histamine on the chemotactic responsiveness of leukocytes from these patients. Histamine caused a small dose-related increase in chemotaxis of neutrophils from both patients and control subjects (10(-7)M to 10(-5)M histamine). In contrast, histamine had no effect on the chemotaxis of monocytes from control subjects but inhibited the chemotactic responsiveness of monocytes from atopic dermatitis patients. These findings suggest that an abnormal sensitivity of monocytes to histamine is an intrinsic feature of atopic dermatitis that may be detectable when the disease is quiescent. Furthermore, this abnormality may contribute to the impairment of monocyte chemotaxis that has been previously observed in patients with active atopic dermatitis.