In previous publications the use of an aerosol time of flight mass spectrometer was reported for the on-line measurements of aerosols (Weiss 1997, Kievit 1995). The apparatus is capable of measuring the size as well as the chemical composition, by the use of Laser Desorption/Ionisation (LDI), of an aerosol particle. A drawback of LDI principle is the direct ionisation mechanism, causing extensive break-up of large biological molecules and thereby losing characteristic information. Interest in, and the ability of, detection of large molecules of biological origin has increased since Matrix Assisted Laser Desorption/Ionisation (MALDI) mass spectrometry has shown that mass spectra of bacteria and spores can be used for identification of bacterial species and even bacterial strains. In MALDI-systems a matrix material has been applied which is able to absorb the energy of an ionisation pulse. The energy is released as heat to the aerosol particle, resulting into a softer ionisation, than is the case by traditional LDI. Combination of aerosol time-of-flight mass spectrometry (ATOFMS) and MALDI-mass spectrometry might therefore provide a tool to investigate the biological origin of the 'Sick Building-syndrome", the biocontent of atmospheric aerosols and become a detector for biological weapons.