Variations in structure and function of peroxisomes in digestive tissues of marine mussels have been proposed to be valid biomarkers of environmental contamination by organic xenobiotics. The aim of the present work was to study the seasonal variations in peroxisomal enzyme activities, catalase, palmitoyl-CoA oxidase (AOX) and D-amino acid oxidase (DAOX) and peroxisomal structure in mussels. Peroxisomal changes were related to the seasonal variation in the contents of neutral lipids in the digestive gland as the lipid metabolism in mussels is subjected to seasonal variations linked to the reproductive cycle and food intake. Significant higher catalase activities were recorded from April to June when compared to the rest of the year and AOX activity was also markedly induced during the late winter and spring (February to May) with maximal activities in April. DAOX activity did not vary seasonally, the highest activities being measured in November, February and May. Stereological studies of peroxisomes in digestive tubule cells revealed significantly higher volume, surface and numerical densities in animals collected in spring and summer. Changes in peroxisomal volume density were found to be significantly and positively correlated with changes in AOX and catalase activities. The peroxisomal structure and enzyme activities were negatively correlated with the lipid contents of digestive tubules. In April, the volume density occupied by neutral lipids was higher in duct epithelia while previously it was higher in digestive tubule epithelia. This trend was maintained during the period in which peroxisomes were more abundant until July. In the following September, digestive tubules recovered their lipid load. It is concluded that seasonal changes related to food intake and reproductive cycle induce changes in peroxisomal parameters that can be compared to typical peroxisome proliferation, with a 25-fold increase in AOX activity and an 8-fold increase in the peroxisomal numerical density in early spring.