An amino acid mixture rich in branched-chain amino acids and poor in aromatic amino acids was infused in six cirrhotics with altered plasma amino acid profile and normal mental state. The effect on muscle protein catabolism, as measured by urinary excretion of 3-methylhistidine, was assessed during two consecutive 3-day periods in which patients received the amino acid mixture alone or in a hypertonic dextrose solution. During a 3-day basal period, cirrhotics showed increased rates of 3-methylhistidine excretion as compared to six matched healthy subjects. Both treatments reduced urinary 3-methylhistidine to normal. During treatment, branched-chain amino acids failed to normalize, plasma aromatic amino acid concentrations and ammonia declined, and alanine increased. Branched-chain amino acids are mainly oxidized in skeletal muscle with production of alanine. Reduced muscle protein catabolism following amino acid infusion is consistent with the physiological role of branched-chain amino acids in suppressing protein breakdown and stimulating protein synthesis. Long-term therapy with branched-chain amino acid-enriched mixtures may prove useful in advanced cirrhotics with severe muscle wasting.