The objective of this study was to determine the effect of alpha-linolenic acid (ALA) supplementation on blood lipids and inflammatory markers, in relation to apolipoprotein (apo) E genotype. The diets of 50 dyslipidemic male patients were supplemented with 15 mL of flaxseed oil per day for 12 weeks. Retrospectively, 3 apo E genotype variants were found (epsilon2/epsilon3, n=7; epsilon3/epsilon3, n=33; epsilon3/epsilon4, n=10). No significant differences were found among apo E genotypes in any variables at baseline. ALA supplementation produced a small but significant decrease in high-density lipoprotein cholesterol (from 1.12 to 1.08 mmol/L, 43 to 42 mg/dL; p=0.008) and apo A-I levels (from 1.28 to 1.24 g/L, p=0.036) in the epsilon3/epsilon3 homozygotes. In addition, ALA supplementation resulted in a significant decrease in the serum concentration of serum amyloid A (SAA) (p=0.014), C-reactive protein (CRP) (p=0.013), macrophage colony-stimulating factor (MCSF) (p<0.001), and interleukin (IL)-6 (p=0.028). Serum SAA and MCSF were also significantly decreased in the epsilon3/epsilon4 group (p=0.005 and p=0.017, respectively). In contrast, ALA produced no effects on any of the inflammatory markers in the epsilon2/epsilon3 group. ALA may have beneficial effects on inflammation in dyslipidemic carriers of the apo epsilon3/epsilon3 and epsilon3/epsilon4 genotypes, but not in carriers of the epsilon2 allele.