This investigation concerns the question of how the size of inhaled aerosol particles influences the rate at which nonvolatile substances are absorbed from the lungs into the bloodstream. Water solutions of non-metabolized "model" compounds will be aerosolized to form liquid aerosols of different particle (droplet) size as defined by the mass median aerodynamic diameter. Anesthetized mice, rats, rabbits and dogs, prepared with a tracheal cannula, will inhale each aerosol by a quantitative exposure method developed in this laboratory, and blood samples will be taken both during and after aerosol exposure. Using standard pharmacokinetic methods of analyzing plasma drug concentration-time relationships, we will then determine the rate of pulmonary absorption for each model compound and each aerosol particle size. Since the distribution of aerosol particles to alveolar, bronchiolar and bronchial regions of the lung is related to the size of the particles, analysis of the above absorption data should give information on the relative permeability of each of these regions to the compounds studied. In addition, since data will be obtained for a series of mammals with lungs of increasing size (mouse, rat, rabbit, dog), it is possible that the results will allow extrapolation to larger animals including man.