Biomarkers are useful tools to study the health of estuarine and marine ecosystems. Biomarkers can be measured in different organisms, but mussels have acquired a global importance as sentinels in marine pollution-monitoring programs. In the present work, we aimed to determine the effects of different endocrine disruptors in mussels by using peroxisome proliferation as a biomarker of exposure to organic pollutants and the levels of vitellogenin (Vtg)-like proteins as biomarker of endocrine disruption. In experiment 1, mussels Mytilus edulis were exposed for 3 weeks to North Sea crude oil (NSO 0.5 ppm) and a mixture of 0.5 ppm NSO, 0.1 ppm alkylphenol mix, and 0.1 ppm extra polycyclic aromatic hydrocarbons (PAHs) (MIX). In experiment 2, mussels were exposed for 3 weeks to diallylphthalate (DAP 50 ppb), bisphenol-A (BPA 50 ppb), and tetrabromodiphenylether (TBDE 5 ppb). Peroxisome proliferation was assessed by measuring acyl-CoA oxidase (AOX) activity and peroxisomal volume density (VVp) in digestive gland. Vtg-like protein levels were measured in gonads by the alkali-labile phosphate (ALP) method. Gonad was also analyzed histologically, and the gonad index (GI) calculated. Mussels exposed to NSO and MIX showed significantly increased AOX activities and VVP compared with control animals. Significantly higher VVP was also found in DAP- and TBDE-exposed mussels. Effects on ALP and GI depended significantly on sex and time of year. In female mussels, ALP levels and GI were lower in the NSO group. In male mussels, ALP levels were significantly increased in the MIX group. The volume density of athretic oocytes was higher in the NSO and MIX exposure groups than in controls, and gonad resorption was observed in the BPA exposure group. Our results confirm the usefulness of peroxisome proliferation as a biomarker of exposure to organic contaminants in mussels and indicate that changes in Vtg-like proteins could be used as potential indicator of pollutant effects on mussel reproduction.