Recently, it has been reported that major and melancholic depression are accompanied by a lower availability of total L-tryptophan (L-TRP) to the brain and by significant changes in electrophoretically separated protein fractions, such as albumin and alpha 2-globulin. The aim of this study was to examine the relationships between serum L-TRP availability and total serum protein, albumin, and alpha 2-globulin in 42 depressed and 24 normal subjects. In depressed and normal subjects, alone and together, there were significant and positive correlations between serum L-TRP and total serum protein or albumin concentrations. In the depressed subjects, but not in normal controls, there were significant inverse relationships between the L-TRP/competing amino acid ratio and the alpha 2-globulin fraction. Serum L-TRP and albumin were significantly lower in melancholic subjects than in normal and minor depressed subjects. Depressed subjects had a significantly lower L-TRP/competing amino acid ratio and significantly higher serum alpha 2-globulin than normal controls. Total serum protein was significantly lower in major depressed subjects than in normal controls. The results suggest that lower L-TRP availability to the brain in depression is related to lower serum albumin and to increased alpha 2-globulin fraction, which are both hallmarks of the acute phase response in depression. the results further corroborate the hypothesis that lowered L-TRP availability in depression is related to the acute phase response in that illness.