The thermal stabilization of human albumin by caprylate (CA) and acetyltryptophanate (AT) was studied by monitoring the formation of albumin polymer (defined as species larger than dimer) on the basis of its molecular size as well as its characteristic migration as α-globulin. Heating 5% protein solutions of purified albumin monomer, Cohn fraction V, and fraction IV-4 + V at 60°C in 0.1 M sodium phosphate or 145 mM sodium chloride, pH 7.0, established the following order of stabilizer effectiveness: 4 mM CA + 4mM AT ≈ 4 mM CA>8 mM AT≥2mM CA>4 mM AT. However, albumin was more thermally stable in the chloride medium. Raising the CA concentration above 4 mM provided little additional stabilization. The D- and L-enantiomers of AT were equally effective, but 16 mM AT was needed to equal the effect of 4 mM CA. L-Tryptophanate exerted only slight stabilization, even at 32 mM\ D-tryptophanate was even less effective. The albumin polymer level increased progressively with time at 60 °C in 2 mM CA or 4 mM AT, whereas in 4 mM CA it reached a plateau in 4-6 h. Acetone drying of albumin-rich fractions was shown to remove nearly all endogenous fatty acid, rendering the protein thermally labile unless sufficient exogenous stabilizer(s) was added. Even in the presence of 145 mM sodium chloride and 4 mM CA + 4 mM AT or 4 mM CA, the stabilizing effect of endogenous fatty acid was still detectable.