This trial was undertaken to assess the safety and efficacy of long-term oral supplementation with branched-chain amino acids as an adjunct to conventional therapy in patients with stable cirrhosis and latent encephalopathy. Latent encephalopathy was diagnosed by psychometric testing, used to assess automobile driving capacity. Seventeen patients with impaired driving capacity received either branched-chain amino acids or placebo for 8 weeks before being crossed over to the other regimen for an equal period. Branched-chain amino acids but not placebo significantly improved psychomotor disturbances (p < 0.01) and driving capacity (p < 0.002). No adverse reactions were observed. We conclude that long-term branched-chain amino acid supplementation is well tolerated and effective in the treatment of impaired automobile driving capacity associated with latent portosystemic encephalopathy.