In this study, we investigated the chemotactic response of a wild-type (N2) nematode (Caenorhabditis elegans) to a water-soluble attractant, sodium acetate, after pre-exposure to the chemical. The chemotactic response to 1.0 M sodium acetate of the non-exposed control nematodes was lower than that of the nematodes that were pre-exposed to 1.0 M sodium acetate for 90 min (p < 0.05). The increase in the response to sodium acetate was observed up to 6 hr, but not at 12 hr after exposure. To clarify the mechanism of this enhancement of the chemotactic response, several mutants were used. The chemotactic response of pre-exposed tph-1 and bas-1 mutants, whose main defect was serotonin secretion, was enhanced in comparison with that of the control mutants (p < 0.01). However, cat-1 and cat-2 mutants, which are respectively defective in serotonin and dopamine secretion and dopamine secretion only, showed no enhancement of the chemotactic response to sodium acetate, even when pre-exposed to this chemical. When the cat-1 and cat-2 mutants were pre-exposed to sodium acetate and bred in the presence of 40 mM dopamine, these mutants showed enhanced chemotactic response to sodium acetate (p < 0.05). These results suggest that the enhancement of chemotactic response to sodium acetate after pre-exposure to this chemical is modulated by dopaminergic neurotransmission.