The association of vitamin A supplementation with concentrations of positive acute-phase proteins in the serum was investigated in the Child Health Study of the Ghana Vitamin A Supplementation Trials, a randomized, controlled trial of the effect of vitamin A on morbidity in children aged < 5 y. Mean serum concentrations of alpha 1-acid glycoprotein, serum amyloid A, and C-reactive protein did not differ overall between the vitamin A-supplemented and placebo-treated groups. Treatment groups were then subdivided according to what symptoms children had experienced in the week before blood sampling. Acute-phase-protein responses to fever and cough were not affected by vitamin A supplementation. There was a tendency for vitamin A-supplemented children, but not placebo children, to have elevated acute-phase proteins in association with reported vomiting or severe diarrhea. The failure of unsupplemented children to mount an acute-phase response may have contributed to their increased morbidity from gastrointestinal symptoms.