We hypothesized that more rapidly growing preterm infants would have higher rates of protein synthesis than term infants, and that protein synthesis would be more closely related to intracellular than plasma levels of amino acids. Neutrophils, used as a cell model, were isolated from 1-3 ml blood of 63 infants 27-44 wk postconceptual age. Protein synthesis (3H-leucine incorporation, pmol/h/mg DNA), and 19 amino acids in the leukocytes (nmol/mg DNA) and plasma (nmol/ml) were quantified. Protein synthesis was related inversely to birth weight and gestational age, i.e. the smaller and more preterm the infant the higher the rate of protein synthesis. Multiple regression analysis limited to six steps indicated that some plasma amino acids (Val, Ile, Phe, Asp, Ala, Tau) accounted for a significant (p = 0.03), but relatively small, proportion, 23%, of the variance in protein synthesis. A greater proportion of the variance in protein synthesis was explained by a set of six intracellular amino acids (Leu, Met, Tyr, Gly, Ala, Tau), with R2 = 36%, p = 0.001. Further, multiple regression identified specific combinations of six plasma amino acids which best explained ("predicted") the levels of each intracellular amino acid predictor of protein synthesis (R2 = 0.4-0.5, p less than 0.001-0.0001). Activities of some rate-limiting glycolytic enzymes, pyruvate kinase and phosphofructokinase, were correlated with protein synthesis in the leukocytes (p = 0.036, and 0.002, respectively). Phosphofructokinase, the major regulating enzyme in glycolysis, also was negatively correlated with birth weight and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)