In the rat, acute stress induces a rapid mobilization of tissue ascorbate, de novo synthesis of ascorbate in liver, and a rise in plasma and urinary ascorbate levels, culminating in elevated total-body ascorbate levels. In human beings, the enhanced metabolism of ascorbic acid after stress results in a rapid fall in ascorbate stores because of the body's inability to synthesize ascorbate in vivo. The physiologic relevance of these changes has not been established, but Chatterjee et al have postulated that ascorbate mobilization during stress may be a natural defense mechanism for the detoxification of excess histamine, an inflammatory substance that is synthesized and released by most tissues in response to chemical, physical, or immunologic stress. Histamine-induced vasodilation and increased vascular permeability promote the "fight-or-flight" response and healing. Excess histamine, however, has a negative impact on circulatory and immunologic homeostasis. Chronic administration of 2 g of L-ascorbate per day has significantly lowered blood histamine levels by 40% in healthy adults; this reduction in histamine was inversely related to leukocyte chemotaxis, a measure of immune responsiveness. In this study, we examined whether 500 mg ascorbate daily, a level that could be obtained in a carefully planned diet, had an antihistamine effect