We have applied nonresonant laser secondary neutral mass spectrometry (Laser-SNMS) to examine different states of biomineralization in vitro. Primary osteoblast-like cells derived from bovine metacarpals were cultured for 5 weeks on clean smooth silicon substrates. For mass spectrometric investigations, the cells and newly formed mineral were cryofixed, freeze-fractured, and freeze-dried. The results indicate that in the vicinity of single osteoblasts, extracellular enrichment of potassium typically occurs during the initial stages of mineralization. Potassium may interact with matrix macromolecules and prevent an uncontrolled apatite deposition. However, apatite biomineral formation is correlated with a potassium release. In conclusion, potassium seems to be involved in the process of extracellular matrix biomineralization. (C) 2004 Elsevier B.V. All rights reserved.