Hydroxyapatite (HA) shows prom ise as a rein forcement phase in synthetic orthopedic bicomposites due to a close resemblance to bone m ineral, as well as de monstrated biocompatibility and bioactivity. Polymers reinforced with HA whiskers have exhibited improved bone-like m echanical properties compared to equiaxed HA powders. Preliminary studies have also indicated that HA whiskers are at least as biocompatible as conventional HA powders. Therefore, the objective of this study was to examine the effects of HA crystal m orphology on osteoblast-like response in two-dim ensional substrates independent of the HA composition, stoichiom etry and porosity. The HA crystal m orphology affected th e substrate surface roughness, which was measured by profilometry. The average roughness of HA whi sker compacts was more than twice that of the powder com pacts. Specific aims of this study were to quantify and compare osteoblast attachm ent, viabi lity, proliferation and differe ntiation in response to HA powder and whisker m orphology. MC3T3-E1 osteoblast-like cells were cultured on HA powder and whisker com pacts for a period of up to 14 days. Cell attachment, proliferation and differentiation were sim ilar on both substrate t ypes, although spreading was greater on HA whiskers. Proliferation did not increase throughout a seven day culture period; however, cells reached c onfluence by 14 days in culture on both substrates. These results, in conjunction with the improved mechanical properties of polymer composites reinforced with HA whiskers, establish whiskers as a biomaterial of similar cytocom patibility to conventional equiaxed HA powders and worthy of further study.