ApoA-IV is a protein constituent of HDL particles; the gene coding for it is a member of the ApoA-I–ApoC-III–ApoA-IV cluster. To investigate the effects of the quantity and the degree of saturation of dietary lipid on the long-term response of this Apo, and on the hypothetical coordinated regulation of the cluster in vivo, pigs were fed isoenergetic, cholesterol-free, low-lipid or lipid-enriched diets (containing either extra olive oil (rich in MUFA) or sunflower oil (rich in n−6 PUFA)) for 42 d. In animals fed on the control diet, ApoA-IV was mainly associated with plasma lipoproteins. An increase in plasma ApoA-IV concentration, mainly in the lipoprotein-free fraction, was induced by the lipid-enriched diets, independent of the degree of saturation of the fatty acids involved. The latter diets also led to increases in hepatic ApoA-I, ApoA-IV and ApoC-III mRNA levels, more so with the sunflower oil-rich diet. The present results show that porcine plasma ApoA-IV levels and their association with lipoproteins are very sensitive to increases in dietary lipids, independent of the degree of fatty acid saturation. Furthermore, hepatic expression of RNA appears to be coordinated along with that of the other members of the gene cluster.