Perfluorochemicals are fluorine-saturated carbon-based molecules which demonstrate utility in the areas of imaging and oxygen delivery. In general, these molecules are biologically inert and, therefore, do not pose toxicologic risk from metabolic degradation. Intravenous (i.v.) perfluorocarbon (PFC) emulsions are cleared from the blood through a process involving phagocytosis of emulsion particles by reticuloendothelial macrophages (RES) and ultimate elimination through the lung in expired air. RES phagocytosis of PFC emulsion particles leads to characteristic, predictable, and reversible biological effects that are a consequence of a normal host -defense mechanism. This mechanism is characterized by dose-related stimulation of macrophages and subsequent release of intracellular products (particularly metabolites of the arachidonic acid cascade and cytokines) which are responsible for most of the biological effects associated with i.v. PFC emulsions (i.e., cutaneous flushing and fever at lower doses, and macrophage hypertrophy and recruitment at higher doses). These biological effects are reversible, and do not result in any permanent tissue alteration, even with prolonged exposure at relatively high doses. The rate of PFC elimination from the RES is proportional to the vapor pressure of the PFC, inversely proportional to molecular weight and positively influenced by lipophilicity. This dose-dependent respiratory excretion occurs with no evidence of metabolic products. Repeated administration of high doses of PFC emulsion may lead to a saturation of the RES-mediatcd clearance capacity, resulting in a redistribution of PFC to non-RES tissues and ingestion by resident or mobile macrophages. This condition is benign with respect to the integrity of the surrounding parenchyma, as well as to the macrophages themselves. Increased pulmonary residual volume (IPRV) due to pulmonary gas (air) trapping, a reversible side effect, has been observed with i.v. doses of PFC emulsion in some animal species. The gross morphological change associated with IPRV is not accompanied by any histological alteration other than the appearance of vacuolated macrophages (characteristic of the normal clearance mechanism) and some minor, increased interalveolar cellularity. Animal lungs affected by IPRV have a normal, pale pink appearance with no visible lesions or signs of edema. The degree of IPRV is dependent on species, PFC dose, and type of PFC administered; PFCs with higher vapor pressures produce the most severe cases of IPRV in sensitive species. Species sensitivity depends upon physiological and morphological characteristics. There is no evidence indicating that IPRV occurs in humans. Although i.v. PFC emulsions may elicit minor untoward effects, these effects are reversible and, at clinically relevant doses, do not pose a toxicologic risk.