Styrene-7,8-oxide (SO), the major in vivo metabolite of styrene, one of the most important plastic monomers worldwide, is classified as carcinogenic in humans and animals. Although the toxic effects of SO have been extensively documented in human lymphocytes, the molecular mechanisms responsible for SO-induced cell damage are still unknown. In the present study, we evaluated the effect of SO on growth and apoptosis, assessed by FACS and gel ladder analysis, in neuronal PC12 cell line. Our results demonstrate that SO triggered PC12 cell apoptosis in a dose- and time-dependent manner. PC12 apoptosis was associated with caspase-3 activation and modulation of the Bcl-2 family proteins. In addition, examination of the cytoskeleton showed that SO induced F-actin depolymerization and a rapid cell rounding before caspase-3 activation, suggesting that the changes in cell shape involving cytoskeletal structure are an early step in the apoptotic pathway. Therefore, SO triggers a complex apoptotic response consisting of a loss of cytoskeletal organization that precedes caspase-3 activation. These mechanisms may represent the molecular basis of the different SO sensitivity to tumor promotion among species and organs.