The biodegradability of cellulose ester derivatives using a degradation assay based on commercially available cellulolytic enzyme preparations was found to depend on two factors : degree of substitution (DS) and substituent size. The esters comprised a series of novel and unusual cellulose derivatives, different in both type of substitution and DS, and were prepared using homogeneous phase reaction conditions. The cellulose esters and acyl substituents ranging in size between propionyl and myristyl and DS values between 0.1 and nearly 3. Biodegradation was assayed by incubation with cellulolytic enzymes from two commercial sources followed by the determination of the concentration of reducing sugars. The rate of cellulolytic enzyme biodegradability (CEB) was found to differ with morphology. Two of three parent cellulose preparations and all cellulose products regenerated from homogeneous phase solution reached 75-80% of their maximum degradability within ca. 7 days of incubation with the enzyme system. The maximum degree of acylation (a) which the enzyme-could tolerate before the polymer became undegradable and (b) which resulted in degradation in excess of 10% by weight ranged from 0.5 to at least 1.0 of a possible maximum of 3, depending on ester type. CEB per unit of DS was inversely related to the number of carbons present in the acyl substituent.