Soft body tissue and gill and mantle microsomal membranes of Mytilus galloprovincialis, were analyzed to assess geographical and temporal effects on fatty acid distribution with special focus on n-3 polyunsaturated fatty acid (PUFA) content. Mussels and plankton samples were collected in April and in October from three locations of the North Adriatic Sea. Plankton fatty acid composition apparently depended both on the sampling site and time and differences referable to temporal features prevailed on the geographical ones. Accordingly, also mussel fatty acid composition appeared to be more effectively modulated by sampling time rather than by sampling location. Membrane fatty acids showed high homeostatic capabilities to reduce effects of exogenous input on cellular organization. Selective capabilities apparently enable mussels to modulate their fatty acid composition combining plankton input, environmental effects on lipid metabolism and physiological requirements. The constantly higher n-3/n-6 ratio in April than in October, shared by fatty acids of plankton, soft tissues and microsomal membranes, confirms the influence of temporal factors in fatty acid modulation. On these bases, late spring is suggested to be the more suitable period for collecting mussels destined for healthy diet of humans or other animals.