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SummaryThe potential cholestatic effect of amino acids and metabolites of tryptophan were evaluated by use of seven daily intraperitoneal injections to suckling and weanling rat pups. Of the amino acids present in parenteral nutrition solutions, only tryptophan (given at a dose of 4 mM/kg) produced a significant ( p < 0.01) elevation of serum cholylglycine (12.8 2 1.0 pM/liter) as determined by radioimmunoassay, compared to 4.9 f 0.4 pM/liter in salinetreated control animals. Total serum conjugates of cholic acid, as determined by radioimmunoassay, were similarly elevated, as was serum alanine aminotransferase. Tryptophan injection resulted in elevated cholylglycine concentrations only at doses of 3 mM/kg/day or higher. Animals more than 2 weeks old did not demonstrate elevation of serum cholylglycine. Injection of lightexposed tryptophan in suckling animals caused a greater elevation of cholylglycine (39.0 f 8.6 pM/liter) than freshly prepared tryptophan solutions ( p < 0.005). Tryptophan and its spontaneous degradation products could contribute to the cholestatic liver changes observed during parenteral nutrition therapy. Abbreviations ALT, alanine aminotransferase ANIT, a-naphthylisothiocyanate AST, aspartate aminotransferase CCA, conjugates of cholic acid CG, cholylglycine TPN, total parenteral nutrition In 197 1, Peden and coworkers (3 1) reported the occurrence of cholestasis in a premature infant receiving parenteral nutrition. More than 20 subsequent reports have confirmed this observation (2) and have suggested lack ofenteral alimentation (4), sepsis (24). and immature hepatic excretory function (35) as possible etiologies. The incidence of cholestasis is related to the duration of parenteral nutrition (I). The rapidity of onset and the severity has been related to the dose of amino acids administered (36). Such observations suggest that amino acids contained in the solutions may be hepatotoxic.Experimental models utilizing perfused rat liver (15,(32)(33)(34), and isolated rat hepatocytes (7) have demonstrated significant cholestatic effects with both individual amino acids and clinically available amino acid solutions. The present investigation was