We present real-time detection of airborne Vaccinia viruses using quartz crystal microbalance (QCM) in an integrated manner. Vaccinia viruses were aerosolized and neutralized using an electrospray aerosol generator, transported into the QCM chamber, and captured by a QCM crystal. The capture of the viruses on the QCM crystal resulted in frequency shifts proportional to the number of viruses. The capture rate varied linearly with the concentration of initial virus suspensions (8.5×108–8.5×1010 particles∕ml) at flow rates of 2.0 and 1.1 l∕min. This work demonstrates the general potential of mass sensitive detection of nanoscale biological entities in air.