Rationale: Little is known about the health effects associated with the inhalation of nanoparticles. The goal was to investigate the fate and inflammatory effects of fluorescent quantum dots (qdots) coated with carboxyl or amine terminal groups after pulmonary exposure. Methods: Male Sprague-Dawley rats were intratracheally-instilled with saline, qdots composed of a Cd/Se core and a ZnS shell with surface carboxyl groups (negatively-charged), or with surface amine groups (positively-charged) on day 0 at a dose of 1.25 or 12.5 micro g/rat. At 2 hr, and on days 1, 3, 5, 7, and 14, the left lungs were cryo-preserved and sectioned for confocal microscopy (LSCM). Bronchoalveolar lavage (BAL) was performed on right lungs, and indicators of lung damage were measured. BAL cells were collected to assess inflammation. Recovered alveolar macrophages (AM) were imaged by LSCM to evaluate cellular uptake of the qdots. Results: At 2 hr after treatment with the high dose, both positively- and negatively-charged qdots were located in the AM, the airspaces, and on the epithelial surfaces, in the alveolar region. By 1 day, localized areas of qdots were observed in interstitial areas of lung parenchyma, and AMs were observed to contain qdots for up to I week. Lung injury and inflammation were elevated over the l4-day time course in the animals treated with the high dose of both forms of the quantum dots compared to controls. At the low dose, detection of qdots in AM and lung tissue was minimal, and little lung injury and inflammation were observed. Conclusions: Fluorescent qdots were imaged within lung cells and tissue using LSCM. AM appear to readily phagocytize qdots in vivo. Instillation of qdots may result in pulmonary inflammation at the high dose non-phagocytized particles deposit in the tissue. Particle surface charge appears to have no effect on lung responses and AM phagocytosis in this animal model.