Apoptosis and proliferation are important causes of adverse health effects induced by inhaled ultrafine particles. The molecular mechanisms of particle cell interactions mediating these endpoints are therefore a major topic of current particle toxicology and molecular preventive medicine. Initial studies revealed that ultrafine particles induce apoptosis and proliferation in parallel in rat lung epithelial cells, dependent on time and dosage. With these endpoints, two antagonistic reactions seem to be induced by the same extracellular stimulus. It was therefore investigated whether proliferation is induced directly by the particles or as a compensation of particle caused cell death. Experimental conditions excluding compensatory proliferation demonstrated that both endpoints are induced independently using specific signaling pathways. Events eliciting signaling cascades leading to apoptosis and proliferation were studied using specific inhibitors of membrane receptors. Epidermal growth factor receptor (EGF-R) kinase activity was identified to be essential for apoptosis as well as for proliferation. As ultrafine particle induced proliferation alone was dependent on the activation of 1-integrins, these membrane receptors are suggested to mediate the specificity of EGF-R signaling concerning the decision whether apoptosis or proliferation is triggered. Accordingly, MAP-kinase signaling downstream of EGF-R showed comparable specificity with regard to receptor dependent induction of apoptosis and proliferation. As key mediators of signaling cascades, the activation of extracellular regulated kinases 1 and 2 (ERK1/2) proved to be specific for proliferation in a 1-integrin dependent manner, whereas, phosphorylation of Jun N-terminal kinases 1 and 2 (JNK1/2) was correlated with the induction of apoptosis.