This study shows that the degradation mechanism and kinetics of monodisperse oligo(lactic acid)s esterified with N-(2-hydroxypropyl)methacrylamide (HPMAm) are strongly influenced by the nature of the chain end. Oligomers with free hydroxyl chain ends degraded predominantly by chain end scission via a backbiting mechanism with a pseudo first-order rate constant k(bb)=2.7 h(-1) in aqueous buffer (37 degreesC, pH 7.2). Once the hydroxyl groups were protected by acetylation, random chain scission became the rate limiting step with k(r)= 0.022 h(-1) under the same conditions. Using these rate constants, the theoretical time-resolved degradation profile was calculated for every (intermediate) degradation product and corresponded very well with the experimental results. The rate of formation of HPMAm was independent of the chain length for the acetylated oligomers, while the hydroxyl terminated oligomers with an even number of lactic acid units formed HPMAm more rapidly than oligomers with an odd number of units. The possibility to fine-tune the degradation rate is relevant when applied as e.g. hydrogels for controlled release or tissue engineering materials. (C) 2004 Elsevier Ltd. All rights reserved.