A comparison was made of the bronchoalveolar lavage fluid (BALF) response to ultrafine nickel (Uf-Ni) and standard-sized nickel (Std-Ni). Rats were intratracheally instilled with 0, 0.1, 0.5, 1 and 5 mg Uf-Ni and Std-Ni, respectively. At 3 d after instillation, the body weight and wet lung weight were determined. At the same time, BALF was analyzed for lactate dehydrogenase (LDH), total protein (TP), tumor necrosis factor-alpha (TNF-alpha), and total cell and differential cell counts. The results showed that indicators of lung injury and inflammation in BALF were markedly raised with increased Uf-Ni and Std-Ni for each from 0 to 1 mg, and there were no differences in the indices between instillation of Uf-Ni at 1 mg and 5 mg. The results also showed that the effects of Uf-Ni on the indices were significantly higher than those of Std-Ni. Additional groups of rats were intratracheally instilled with 1 mg of Uf-Ni or Std-Ni, and wet lung weight and BALF profiles were analyzed at 1, 3, 7, 15 and 30 d later. The effect of Uf-Ni and Std-Ni on indices that can be presumed to reflect epithelial injury and permeability (LDH or TP), and release of proinflammatory cytokine (TNF-alpha) were increased throughout the 30 d post-exposure and the effects of Uf-Ni on these indices were significantly higher than those of Std-Ni from 1 to 30 d after instillation. Moreover, the number of neutrophils and LDH activity in BALF of rats after exposure to Uf-Ni were significantly greater than those of Std-Ni-exposed rats up to 30 d after instillation. Our findings suggest that Uf-Ni has a much more toxic effect on the lung than St-Ni, but the mechanism remains to be elucidated.