The environmental contamination caused by heavy metals raised the question of how environment and biological systems may be affected by metal pollution. Among the bioindicators useful to monitor the toxicological effects of these chemicals, Cnidarians have not been fully considered. Cnidarians possess high specialized stinging cells, termed nematocytes, whose cell volume regulation capability under hyposmotic shock (Regulatory Volume Decrease, RVD) as an essential homeostatic parameter, has been already assessed. The purpose of this report is to verify whether RVD in nematocytes isolated from tentacles of the jellyfish Pelagia noctiluca, collected in the Strait of Messina (Italy) is affected by Artificial Sea Water (ASW) containing heavy metals as Cd²⁺, La³⁺, Co²⁺, Cu²⁺ and Zn²⁺ (100-50 mM). Nematocytes, isolated by applying 605 mM NaSCN plus 0.01 mM Ca2+, were subjected to 65% ASW in presence of heavy metals. Treatment with Co and La inhibited RVD mechanisms but not the osmotic phase, while this latter was prevented by Cu²⁺, Cd²⁺ and Zn²⁺. These results suggest that: i) nematocytes RVD may be affected by pollutants like heavy metals, with consequences on specimens viability, though further studies are needed to clarify the mechanisms whereby heavy metals exert their toxicity at a cellular and intracellular levels; ii) Cnidarians could be considered as a model for ecotoxicological investigations.