Plasma vitamin A, retinol-binding protein, and prealbumin concentrations have been studied in 38 northern Thai children with protein-calorie malnutrition (PCM). The 4-week study period consisted of 1 week of stabilization followed by 3 weeks of treatment with formula diets varying in their protein and calorie content. The stabilization period comprised 7 days of initial treatment with fluids, antibiotics, and a gradually increasing intake of protein and calories to a final level of 1 g protein and 100 kcal/kg of body weight. During this period vitamin A, retinol-binding protein and prealbumin levels all showed significant increases compared to admission values, whereas plasma albumin and total protein did not change. During the subsequent 3 weeks, the effects of four different dietary regimens, with daily calorie and protein intakes of 100 or 175 kcal/kg and 1 or 4 g/kg, respectively, were studied. Significant increases in plasma total protein concentration were seen in each of the four test groups, and increases in plasma albumin and prealbumin were also seen in three of the four test groups, and increases in plasma albumin and prealbumin were also seen in three of the four test groups (all but the 175 kcal-1 g protein group). Significant increases in plasma vitamin A levels were not seen in any of the groups. The higher protein regimens (4 g/kg per day) resulted in much greater increases in plasma albumin and total protein levels than did the lower protein regimens. No significant differences in the changes in retinol-binding protein or vitamin A levels were apparent between the test groups. Sixteen additional children with both clinical vitamin A deficiency and protein-calorie malnutrition showed significant increases in total plasma vitamin A concentrations 24 hours after the intramuscular injection of 100,000 IU water-miscible vitamin A palmitate, without a change in plasma retinol-binding protein concentrations. These studies demonstrate that plasma retinol-binding protein and prealbumin concentrations are more rapidly responsive and sensitive to dietary protein intake than is plasma albumin concentration. Furthermore, the absence of a 24-hour rise in plasma retinol-binding protein after parenteral vitamin A provides further evidence that hepatic retinol-binding protein synthesis is impaired in protein-calorie malnutrition.