A new method is presented for the preparation, characterization and use of PbS (galena) nanoparticles within an in vitro bioaccessibility test representing the respiratory tract, specifically the conditions occurring in conjunction with phagocytosis by cells using artificial lysosomal fluid. Particle production through nanosecond laser ablation enables their rapid production with a relatively narrow particle size distribution, and a diameter enabling them to represent particles that can enter the alveolar region of the respiratory tract (<3 mu m). The PbS nanoparticles were characterized by cascade impaction to define their particle size distribution and through the use of X-ray diffraction (XRD) and electron microprobe analysis (EMPA) to define their mineralogy and homogeneity respectively. The particles were collected via liquid impingement in artificial lysosomal fluid and the undissolved material was separated via ultrafiltration after a contact time of 7-140 hours to define the bioaccessibility. The particles produced by the laser ablation of PbS have a homogenous composition and are 0.083-0.75 mu m in diameter, spherical, crystalline, and have the same stoichiometry as the target material. Despite the low solubility constant of PbS in water (K(sp) = 3.4 x 10(-28)), 53% +/- 2.25 (SD) (n = 3) of the Pb was leached after ca. 48 hours, at which point equilibrium is reached. The competing effects of citrate and tartrate in the artificial lysosomal fluid are responsible for this high level of bioaccessibility. Nanoparticles of PbS display a level of bioaccessibility within human lungs that suggests they represent a significant risk to human health through the inhalation pathway as a result of phagocytosis, although this needs to be supported by in vivo tests.