To investigate the effect, if any, of the acute-phase response on blood vitamin concentrations and to test the hypothesis that these concentrations may change during stress. Open study, utilizing a volunteer sample of patients. Tertiary care center. Twenty-six healthy adult volunteers (14 female and 12 male); 25 volunteers underwent uncomplicated orthopedic surgery and one suffered traumatic limb fractures. None. The presence of a systemic acute-phase response was documented by the determination of serum C-reactive protein concentrations. Blood vitamin concentrations were determined from sequentially collected blood samples over a 7-day period, and compared with entry values. The presence of the acute-phase response was documented by significant and transient increases in C-reactive protein values. This response was accompanied by significant and transient decreases in the concentrations of leukocyte vitamin C, and in plasma concentrations of vitamin A, retinolbinding protein, vitamin E, total lipids, pyridoxal-5' -phosphate, and albumin. Blood concentrations of pyridoxal-5-phosphate, retinal-binding protein, and leukocyte vitamin C decreased to values below the respective normal ranges. These concentrations normalized without any therapeutic interventions. We demonstrated transient, but significant, decreases in blood vitamin concentrations during the acute-phase response. Recommendations regarding daily supplementation with these vitamins in clinical practice cannot be made on the basis of these results, as the functional importance of these observations is not, at present, clear. However, what is clear is that biochemical vitamin concentrations, determined during the acute-phase response, should be interpreted with care.