Bivalves were shown to contain significant levels of manganese (Mn) and vanadium (V) at polluted sites. The purpose of this study was to examine and compare the toxicity and mode of action of Mn and V to Mya arenaria clams. Clams were exposed to increasing concentrations of MnCl₂ and VCl₂ for 120 h at 15 ^oC. After the exposure period, clams were analyzed for Mn and V in tissues along with a suite of biomarkers to appraise energy status (glucose, acetoacetate, esterase and lipids), oxidative stress (peroxidase activity, NO₂ and antioxidant potential), damage (DNA strand breaks, heme degradation and protein aggregation) and neural activity (serotonin and melatonin). In clams exposed to Mn, tissue levels of this element were associated to changes in melatonin, serotonin, protein aggregation, NO₂ levels, oxidative stress (peroxidase), bilirubin and DNA strand breaks in the digestive gland. In clams exposed to V, oxidized V in tissues were associated to peroxidase activity, bilirubin, glucose, serotonin/melatonin levels and DNA strand breaks. However, the melatonin/serotonin ratio was significantly reduced in clams exposed to Mn only suggesting that clams were in an active phase. Discriminant function analysis revealed that Mn and V toxicity profiles were well separated and involved the above biomarkers related to Mn or V in tissues. In conclusion, clams contaminated by Mn and V have the potential to produce various toxic effects at energy status, oxidative stress and neurological levels and these contaminants should be followed more closely.