Abstract To test the hypothesis that the chemical composition and physical properties of an enzyme determine its rate of degradation in vivo, the tyrosine aminotransferase (EC 2.6.1.5) of cultured H-35 cells was induced in the presence of amino acid analogs. Supplementation of tryptophan-free medium with 4-, 5-, or 6-fluorotryptophan yielded enzymes which at 64° denatured 1.2-, 2.2-, or 4.7-fold, respectively, more rapidly than the native enzyme. The degree of change in heat stability was concentration-dependent for each analog. Immunochemical titration revealed that the fluorotryptophan-containing enzyme also had less catalytic capacity per molecule than the native enzyme. With a double isotope technique the rates of degradation of the native enzyme and the 6-fluorotryptophan-containing enzyme were measured simultaneously; both aminotransferases were degraded with half-lives of about 2 hours. Hence, an analog-induced change in physical properties, sufficient to cause marked alteration in heat stability and catalytic capacity, did not change the rate of enzyme degradation in vivo.