In this study, we have prepared poly(beta-hydroxybutyrate), PHB, random stereocopolymers from beta-butyrolactone, BL, using a diethylzinc/water (1.0/0.6) catalyst system. (R)- and (S)-BL were synthesized in high enantiomeric purity (> 98% ee (enantiomeric excess)), and approximately 5% racemization occurred at the methine stereocenters upon polymerization. The PHB stereoisomers produced had R repeat unit compositions of 95, 90, 85, 81, 77, 67, and 50%. In addition, a 50% (R)-PHB stereoisomer with a predominantly syndiotactic repeat unit placement was prepared in our laboratory. The relative degradability of these PHB stereoisomers was studied with a PHB depolymerase enzyme isolated from Penicillium funiculosum. This enzyme has been shown to catalyze the hydrolysis of (R)-PHB, but does not show activity for the enantiomeric substrate (S)-PHB. The P. funicolusum depolymerase/PHB stereocopolymer system, therefore, allowed the study of two opposing effects on the degradation rate: the increase due to the disruption of the crystalline phase, and the decrease due to a stereochemical enzyme impediment, as the (S)-HB content of PHB is increased from 0 to 50%. The initial surface degradation rates in [H+]/(mm2.min) were determined by measuring the pH change as a function of time for polymer/enzyme incubations. It was shown that for R stereocopolymer compositions of 95, 90, 85, and 81% the degradation rate values (between 0.57 x 10(-8) and 0.92 x 10(-8) [H+]/(mm2.min)) were lower than those measured for a 100% (R)-PHB sample (1.41 x 10(-8) [H+]/(mm2.min)) of similar molecular weight. Therefore, the preference for (R)-HB repeat units appears to dominate over crystalline morphology effects for the compositional range of 81-100% (R)-HB. However,the initial surface degradation rates for the 67 and 77% (R)-PHB samples were 2.85 x 10(-8) and 7.51 x 10(-8) [H+]/(mm2.min), respectively, showing dramatically larger rate values compared to that for 100% (R)-PHB. This result suggests that, at a critical degree of disruption of the crystalline order which occurred for compositions between 77 and 81% (R)-HB, effects of crystalline morphology dominate. The noncrystalline 50% (R)-atactic-PHB sample displayed an initial degradation rate which was slightly higher than that observed for crystalline bacterial 100% (R)-PHB. However, this initial observed rate was followed by an abrupt decrease in the rate which was probably due to depletion of (R)-HB-rich segments on the polymer surface. Results from substrate/exoenzyme incubations up to 21 days further confirmed that the 50 % (R)-atactic-PHB sample was a poor substrate for the enzyme after the rapid initial degradation of (R)-HB-rich polymer chain segments at the film surface. In contrast, a significant portion of the polymeric chains for both the predominantly syndiotactic 50% (R)-PHB and the 77% (R)-PHB were degraded by the P. funiculosum esterase to products containing on average 3 +/- 1 HB repeat units. The relative degradability of these PHB stereoisomers has interesting implications on the acceptability of specific stereochemical sequences in the degradation of the PHB by P. funiculosum and other PHB depolymerases.