Adaptive response to neurotoxicity on locomotion behavior by severe metal exposure was investigated in Caenorhabditis elegans. Exposure to 2.5μM of metals induced a moderate but significant reduction of locomotion behavior and induction of hsp-16.2::gfp expression. After pre-exposure to 2.5μM of metals, the reduced locomotion behavior induced by subsequent 50 and 100μM of metal exposure were significantly prevented, and the induction of hsp-16.2::gfp expression caused by subsequent 50 and 100μM of metal exposure were significantly suppressed. In contrast, after pre-exposure to 50μM examined metals, the reduced locomotion behavior induced by subsequent 50 and 100μM metal exposure were further decreased, and the noticeable induction of hsp-16.2::gfp expression caused by subsequent severe metal exposure were further enhanced. Therefore, pre-treatment with mild metal exposure can activate the adaptive response to neurotoxicity on locomotion behavior induced by subsequent severe metal exposure in nematodes.