Chronic inhalation of hard metal particles can produce an interstitial lung disease (hard metal disease). Recent studies on rats and on isolated alveolar and peritoneal macrophages have demonstrated that this disorder can be explained by an interaction between cobalt metal (Co) and tungsten carbide (WC) particles, which represent the main constituents of hard metal. The exact mechanism of this interaction is still undefined. The present study was undertaken to assess in vitro whether a similar interaction also occurs between cobalt and other metallic carbide particles which may also be incorporated in hard metals depending on the desired applications. When tested separately, Co and metallic carbide particles did not affect the cell integrity. In contrast, TiC, NbC and Cr(3)C(2) exerted a synergistic effect with Co (interactive carbides) while TaC, Mo(2)C and SiC did not (non-interactive carbides). The interaction did not simply result from an increased cobalt bioavailability since cobalt uptake by the macrophages was increased 4-7-fold in the presence of interactive as well as non-interactive carbides. The interactive effect appeared dependent on the size of the carbide particles, which suggests that a physicochemical reaction taking place at the interface between certain carbides and cobalt particles may be responsible for the toxicity of the Co-carbide mixture. Other non-carbide particles (Fe, diamond, crystalline silica) did not produce a similar interaction with cobalt. This observation may contribute to the better delineation of the pathogenesis of hard metal disease.