The uptake of respirable quartz particles by alveolar macrophages (AM) is believed to cause an inflammatory response, which is discussed as a crucial step in quartz pathogenicity. However, little is known about the mechanism and the relevance of particle uptake. Therefore, the aim of this study was to analyze the role of the actin cytoskeleton in quartz particle uptake, reactive oxygen species generation (ROS) and tumour necrosis factor alpha (TNF-alpha) release. Primary rat alveolar and interstitial macrophages (IM) as well as a rat alveolar macrophage cell line (NR8383) were treated with quartz particles at various concentrations and time intervals. Particle uptake was studied using flow cytometry and light/fluorescence microscopy to analyze particle uptake and cytoskeleton recruitment. Intra- as well as extracellular ROS generation was analyzed by flow cytometry and electron spin resonance (ESR). Flow cytometric investigations demonstrated a dose- and time-dependent particle uptake. Primary AM showed a similar uptake indicating that the cell line provides a good model to investigate the mechanisms of particle uptake while primary IM had a lower uptake rate. Inhibition of actin polymerization using cytochalasin-D caused a significant reduction of particle uptake in NR8383 cells. The quartz induced dose-dependent increase of ROS generation and TNF-alpha release was also blocked by inhibition of actin polymerization. Our results demonstrate an active involvement of the cytoskeleton in uptake of quartz particles and suggest a role of the actin framework and/or the particle uptake in DQ12-induced ROS generation and cytokine release.