We have examined atomic and molecular distributions in freeze-fractured freeze-dried primary osteoblasts and cancer cells using time-of-flight secondary ion mass spectrometry (TOF-SINIS) and non-resonant laser secondary neutral mass spectrometry (NR-Laser-SNMS). A pulsed Ga primary ion beam with a diameter of approximately 200 nm was employed to bombard the sample. Ion-induced electron-images were used to identify individual cells. High resolution elemental and molecular images were obtained from cell cultures. From these data the K/Na ratio was determined. It shows a higher K-concentration inside individual cells demonstrating that the chemical and structural integrity of living cells were preserved by the applied preparation technique. Consecutive presputtering of the sample with different primary ion dose densities was used to move the analysis plane toward the inside of the cell. It can be concluded that TOF-SINIS and Laser-SNMS are well suited for imaging trace element and molecule concentrations in biological samples. (C) 2002 Elsevier Science B.V. All rights reserved.