Unusual dynamic factors affecting the behavior and fate of inhaled cigarette-smoke particles and mineral fibers within the human lung are addressed. The actions of interception, for fiber particles, and cloud-settling, for concentrated cigarette smoke, can enhance focal deposition in locations that would not have been anticipated for dilute aerosols or for more regularly shaped, sphere-like particles. It is important to quantitate the efficiencies of these deposition mechanisms because it is after deposition that deleterious biological effects can occur. Theoretical deposition models are presented that simulate the actions of the interception and cloud-settling processes, which are validated by comparisons with in vitro and in vivo data. The sites of preferential deposition are regions whose cells receive increased doses of hazardous substances associated with smokes and fibers. They must, therefore, be considered in risk assessment analyses of human inhalation exposures to airborne toxicants. Incorporation of these mechanisms in aerosol therapy protocols could conceivably lead to improved therapeutic procedures.