Effects of ZnO NPs and ionic Zn on germline apoptosis and the regulation of genes in the apoptosis pathway were investigated in vivo using the model organism Caenorhabditis elegans.Age synchronized Bristol N2 worms were exposed to ZnO NPs and ZnCl 2 at concentrations of 6.14 Â 10 À1, 61.4, and 614 lM form larval stage 1 (L1) to early adulthood. Possible ZnO nanoparticles were observed under the worm cuticle and also in the gonadal region by transmission electron microscopy (TEM). ZnO NPs and ZnCl 2 both significantly increased the number of apoptotic cells as compared with controls in the 61.4 and 614 lM treatment groups (P < .05). However, ZnO NPs induced more apoptotic cells in the 61.4 lM treatment than ZnCl 2 (P < .05), suggesting ZnO NP is more potent in inducing apoptosis at specific exposure concentration. Findings using the MD701 (bcIs39 [(lim-7)ced-1p::GFP þ lin-15(þ)]) strain further confirmed the observations in N2 strain. Genes involved in the apoptosis pathway (ced-13, ced-3, ced-4, ced-9, cep-1, dpl-1, efl-1, efl-2, egl-1, egl-38, lin-35, pax-2, and sir-2.1) were in general upregulated in response to ZnO NP exposure. The cep-1/p53 gene was up-regulated in gene expression assay. In the cep-1 loss of function mutant, no significant increase in apoptosis was observed. Therefore, the increased apoptosis resulting from ZnO NPs exposure is likely cep-1/p53 dependent. This study provides evidence that ZnO nanoparticles affect germ cell apoptotic machinery as a potential mechanism of reproductive toxicity.