Renewed interest in the antihistamine action of ascorbic acid has emerged with the recently recognized immunosuppressive role of histamine. We examined the antihistamine effect of acute and chronic vitamin C (VC) administration and its effect on neutrophil chemotaxis in healthy men and women. In the chronic study, 10 subjects ingested a placebo during weeks 1, 2, 5 and 6, and 2 g/day of VC during weeks 3 and 4. Fasting blood samples were collected after the initial 2-week period (baseline) and at the end of weeks 4 and 6. Plasma ascorbate rose significantly following VC administration compared to baseline and withdrawal values. Neutrophil chemotaxis rose 19% (NS) during VC administration, and fell 30% after VC withdrawal, but these changes were not correlated to plasma ascorbate levels (r = 0.01). Chemotaxis was inversely correlated to blood histamine (r = -0.32, p = 0.045), and, compared to baseline and withdrawal values, histamine levels were depressed 38% following VC supplementation. Blood histamine and neutrophil chemotaxis did not change 4 hours following a single 2 g dose of ascorbic acid, although plasma ascorbate rose 150%. These data indicate that VC may indirectly enhance chemotaxis by detoxifying histamine in vivo.