The mouse fibroblast cell line L929 was inoculated on 3D scaffolds of microbial polyesters, namely polyhydroxybutyrate (PHB) and poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) to evaluate their in vitro biocompatibility. It was found that both polyhydroxyalkanoates (PHA) subjected to lipase treatment and hyaluronan (HA) coating decreased the contact angle of water to the material surface approximately 30%, meaning an increased hydrophilicity on the PHA surface. At the same time, both the lipase treatment and the HA coating smoothened the PHA surface. After the lipase treatment or HA coating, the ratio of PHA hydrophilic groups including hydroxyl and carboxyl to carbonyl of PHA was approximately 1:1 or 2:1. Cells grown on scaffolds treated with lipase were approximately 4 x 10(5)/ml, twice in number of the control. However, PHA scaffolds coated with HA were observed with a 40% decrease in cell growth compared with that of the control. HA coating reduced the cell attachment and proliferation on PHA although the materials had increased hydrophilicity. In comparison, lipase treatment promoted the cell growth on PHA although the treatment did not lead to better hydrophilicity compared with HA coating. It appeared that an appropriate combination of hydrophilicity and hydrophobicity was important for the biocompatibility of PHBHHx, especially for the growth of L929 cells on the surface of this material. This may have instructive significance for biomaterial selection and design.