Abstract Male and female F344 Lov rats were exposed to aerosols produced by burning lithium metal under conditions designed to stimulate a fire in the containment building of a fusion reactor. Lithium combustion aerosols were generated by sweeping lithium vapor into air atmospheres with controlled CO 2 and H 2O concentrations. Chemical analyses of the aerosols produced indicated a dependence of the chemical form of carbon dioxide concentrations and relative humidity. Under conditions of low CO 2 concentration and low relative humidity (<25%), the aerosol was predominantly lithium monoxide with some lithium hydroxide and about 12% lithium carbonate. Under conditions of high relative humidity (>75%), the aerosol was primarily lithium hydroxide with about 23% lithium carbonate. Although these two aerosols might be expected to have different acute toxicities based on their differing alkalinities, the 14-day LC50 values (with 95% confidence limits) determined after 4-hr exposures were 940 (730–1200) mg/m 3 for the lithium oxide and hydroxide mixture and 960 (830–1200) mg/m 3 for the lithium hydroxide aerosols. Histopathologic lesions were observed in the nasal turbinates, larynx, and occasionally in the lungs with both aerosols. The most prominent lesions were necrotizing laryngitis and ulcerative rhinitis. Pulmonary lesions represented a secondary extension of the upper respiratory tract lesions rather than a primary manifestation of lithium toxicity. The similarities in the LC50 valus and also in the histopathologic lesions observed suggest that any Li 2O in the aerosol reacted rapidly with water vapor in the respiratory tract to form LiOH prior to deposition.