Homopoly(L-lactide) and homopoly(D,L-lactide) were almost inert for biodegradation with tricine buffer or normal enzymes such as bromelain, pronase, and cholesterol esterase but biodegradable with proteinase K. Significantly enhanced biodegradation was observed when an optically active (R)- or (S)-3-methyl-4-oxa-6-hexanolide (MOHEL) unit was introduced into poly(L-lactide) [poly(L-LA)] or poly(D,L-lactide) [poly(D,L-LA)] sequences. Poly[L-LA-ran-(R)-MOHEL] in molar ratios of 86/14 to 43/57 showed good biodegradability that was independent of crystallinity. The biodegradation of polymers with proteinase K increased in the following order: poly[D,L-LA-ran-(R)-MOHEL] > poly[L-LA-ran-(R)-MOHEL] > poly[D,L-LA-ran-(S)-MOHEL] > poly[L-LA-ran-(S)-MOHEL] > poly(R)-MOHEL > poly(D,L-LA) The number-average molecular weight, molecular weight distribution, glass-transition temperature, and melting temperature did not change before and after the biodegradation of poly[L-LA-ran-(R)-MOHEL], indicating that the degradation occurred from the polymer surface.