In the present study we report results on the possible mechanism of inhibition of tryptophan-5-hydroxylase activity induced by insulin-dependent diabetes mellitus (IDDM). Kinetic experiments were done with different L-tryptophan (L-Trp) concentrations in the rat brain at different days of evolution of the disease. Additionally, different activation conditions of the enzyme were evaluated, to gain information on the mechanism of the activity changes. Diabetes state was induced in normal male rats, by the administration of 75 mg/kg body weight of streptozotocin (STZ). The results showed an increase of the Km value and a decrease in the Vmax in the diabetic's brain as compared to controls. Interestingly, in the diabetic group, the response capacity to phosphorylation is significantly reduced. These shifts in the activity of tryptophan-5-hydroxylase developed during IDDM may not be explained only by a decrease of L-Trp, but also by a possible change in the enzyme itself, reflected in a diminished affinity for the substrate and a decreased response to phosphorylating conditions.