Diabetic ketoacidosis (DKA) is a severe metabolic disturbance of insulin-dependent diabetes mellitus (IDDM) which has a significant effect on amino acid metabolism. Amino acids serve as precursors for various neurotransmitters which are involved in affective disorders, and patients with IDDM are known to have an increased prevalence of affective disorders. We monitored the plasma concentrations of 23 amino acids in six adolescents prior to treatment of DKA and at 6, 24 and 120 hours after initiation of treatment. The well-known increase in the concentrations of the glucogenic amino acids and the decrease in the branched-chain amino acids were observed in response to treatment of DKA. Low levels of tryptophan were found prior to treatment of DKA. Treatment increased the plasma tryptophan levels, but the mean concentration remained low throughout the sampling period. Only the glutamate-derived amino acids (glutamate, proline and glutamine) from the Krebs cycle pool were significantly affected by treatment. Glutamine declined initially, but recovered as the plasma pH normalized. Our results indicate that DKA causes a depletion of plasma tryptophan. This depletion may predispose some patients with IDDM to have affective disorders secondary to a neurotransmitter imbalance.