Evidence from several sources suggest that blood-brain transport of the large neutral amino acids (NAA) is abnormal in animals with a portacaval anastomosis (PCA) and in patients with liver cirrhosis and portal-systemic shunting and encephalopathy, but the underlying mechanisms are unknown. After PCA, the concentration of glutamine (Gln) in brain is markedly increased as a by-product of cerebral ammonia detoxification, and the rate of efflux of Gln from brain is also increased. The following studies were undertaken to clarify the relationships among plasma and brain concentrations of NAA after PCA in rats and to examine the relationship of brain Gln concentration to plasma and brain NAA concentrations. After PCA plasma phenylalanine, tyrosine and histidine were elevated and leucine, isoleucine and valine were lowered. In brain, phenylalanine, tyrosine, histidine and methionine were markedly elevated after PCA and their concentrations in brain far exceeded the concentrations in plasma. Analyses of single, partial and multiple correlations of plasma NAA ratios expressed as plasma competitor function (PCF), brain NAA and brain Gln showed significant correlations between PCF nd brain NAA in shunted rats. A better correlation was found between brain NAA and brain Gln. Correlation coefficients obtained from multiple correlation analysis equalled or exceeded those obtained in the partial correlation or in the single correlation, suggesting that the effects of PCF and brain Gln on brain NAA were separate and additive. Gln was shown to compete with other NAA for blood brain transport by inhibiting brain 14C phenylalanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)