AbstractLysosomes are cell organelles containing hydrolytic enzymes and involved in intracellular digestion. Numerous environmental contaminants can interfere with lysosomes, and the purpose of the present work was to quantify changes induced by petroleum hydrocarbons on the structure of the lysosomal system of mussel digestive cells. Mussels,Mytilus galloprovincialisLmk., were exposed for three months to the water accommodated fraction (WAF) of two crude oils (URAL and MAYA) and of a lubricant oil. Three different exposure doses (0.6, 6, and 40% WAF) were used for each type of hydrocarbon and mussels were sampled at different time intervals (days 21, 49, and 91). A stereological study, using an automated image analysis system, was made on sections stained for demonstration of β‐glucuronidase activity and four parameters were calculated: lysosomal volume density, surface density, surface to volume ratio, and numerical density. The results indicate that the effect of the exposure dose on lysosomal structure is variable and there is no linear relationship of lysosomal changes with dose. Regarding the effect of the exposure time, two different responses were evidenced: (a) a short‐term response (at day 21) with a decrease in size and numbers of lysosomes and (b) a long‐term response (at days 49 and 91) with an increase in lysosomal size and a decrease in their numbers. The short‐term response may be due to a disintegration process of the digestive cells with subsequent loss of lysosomes and could represent an adaptative response to hydrocarbon exposure. At long exposure times, lysosomal changes, apparently caused by fusion processes giving rise to enlarged lysosomes, correspond to a “general stress response”. ©by John Wi