Bombyx mori silk fibers were chemically modified with various kinds of isocyanates and diisocyanates, including phenyl isocyanate and hexamethylene diisocyanate. The reactivity of these modifying agents toward silk fibers was examined as a function of the reaction solvent, temperature, time, and isocyanate chemistry. The use of DMSO as the solvent, bifunctional isocyanates, such as hexamethylene diisocyanate, and a temperature of 75 degreesC resulted in higher weight gains of modified silk fibers. The physical and chemical properties of the modified silk fibers were studied as well. The moisture regain tended to decrease as the weight gain increased, the extent depending on the kind of isocyanate used. The resistance of silk toward attack by hot acid and alkali was generally enhanced by a reaction with isocyanates, the only exception being phenyl isocyanate, which induced a drop of alkali solubility. The tensile strength remained almost unchanged, regardless of chemical modification, while elongation at break decreased. The optical properties and the thermal stability of the modified silk fibers were not influenced by the reaction with isocyanates, suggesting that the fine structure of silk remained unchanged, regardless of chemical modification.