The presence of biological molecules can significantly regulate the crystallization of inorganic hard tissues in living organisms. The purpose of this study is to investigate the influence of fetal bovine serum (FBS) on the precipitation and phase transformation of calcium phosphate. The precipitation of large-sized calcium phosphate in RPMI1640, a widely used cell culture, is readily induced by an addition of calcium solution. However, FBS can retard this unexpected calcification process in RPMI1640. Using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy, it is revealed that FBS can suppress the aggregation of nano-calcium phosphate clusters. Furthermore, FBS can also retard the phase transformation of unstable amorphous calcium phosphate to crystallized hydroxyapatite in biological milieus. The results show that FBS has a very strong negative influence on the precipitation of calcium phosphate, which plays an important role in stabilizing the blood compositions. This study also implies the application of FBS in the treatment of pathological calcification. (C) 2008 Elsevier B.V. All rights reserved.