Chronic inhalation of slightly soluble, inhalative dust causes lung damage such as acute inflammation, fibrosis and carcinogenesis. In this context, alveolar macrophages are considered to be primarily responsible for these hazardous dust effects. Particle phagocytosis stimulates the synthesis and release of mediators (cytokines, growth factors ...) which coordinate severe inflammatory reactions, resulting in hypoxic conditions and formation of fibrous connective tissue in the lung parenchyma. Currently, the toxicity of inhalative dust is assessed exclusively in inhalation experiments in vivo using animal models. To create a cell culture based in vitro model, which allows the reproducible assessment of hazardous particles, we examined the three established macrophage cell lines RAW 267.4 (mouse), NR8383 (rat) and THP-1 (human) with regard to activation and cytokine expression. Therefore we stimulated these cells with either bacterial lipopolysaccharides (LPS) or samples of control dusts of known toxicity (quartz DQ12 and elctro corundum). Alterations in gene expression of inflammatory cytokines were measured by RT-PCR. We were able to confirm the induction of the proinflammatory cytokines IL- 1b, IL-6; MIP-2a and TNFa in all three cell lines after stimulation with LPS. Furthermore, the time course of LPS induced cytokine expression was comparable between the cell lines. Exposure to low concentrations of soluble, inhalative dust particles showed only slight effects with respect to activation and cytokine expression. Thus we assume that a short time exposure to highly toxic dust at low doses has no substantial effects on macrophages.