Crustaceans can store excess copper in the hepatopancreas, an organ playing a role in digestive activity as well as in neurosecretory control. Here, we studied the effect of copper exposure on the level of histamine, an indicator of food spoilage in edible crustaceans. Histamine is also a neuromodulator in the intestinal nervous system of crustaceans, and a human allergen. Marbled crayfish (Procambarus fallax forma virginalis) were exposed to average measured values of 0.031 mg Cu/l and 0.38 mg Cu/l, respectively, for 14 days and then transferred to copper-free water for another 14 days. Concentrations of copper and histamine in the hepatopancreas and muscle were evaluated at different time points. Histamine levels were significantly higher in hepatopancreas and muscle tissues at the highest exposure level, but only after transfer of the animals to copper-free water. The increased histamine concentration following copper exposure may be explained by a (delayed) stress response, and by up-regulated histidine synthesis induced by copper, followed by decarboxylation to histamine. © 2012 Koninklijke Brill NV, Leiden.