Two biochemical distinct groups of manic depressive patients seem to be present. One group showed a normal pattern of plasma amino acids and was resistant to oral tryptophan medication. Another group, characterized by a relative deficiency of tryptophan in plasma as measured by the ratio of total plasma tryptophan to competing amino acids, responded readily to tryptophan treatment. No significant differences could be demonstrated in the free tryptophan, total tryptophan, percentage of free tryptophan or kynurenine in the plasma between patients and controls. The findings are discussed in view of changes in the transport conditions of tryptophan from plasma into the brain.