Five SNPs in the CD36 gene, 25444G>A, 27645del>ins, 30294G>C, -31118G>A and -33137A>G in haplotypic combinations, link to fasting plasma NEFA concentrations. Fish oil lowers TAG concentrations. The influence of CD36 SNPs on hypotriglyceridemic effects is unknown. The study examines how four of the SNPs modify the effects of fish oil on fasting plasma TAG, NEFA, glucose LDL and HDL cholesterol concentrations in 111 healthy, middle-aged, Caucasian men. Subjects consumed habitual diets while taking 6g MaxEPA daily for 12 weeks. TAG decreased from 1.48 mol/l to 0.11 mmol/l, and glucose and HDL rose from 5.92 to 0.15 mmol/l and from 1.27 to 0.04 mmol/l, respectively, irrespective of genotype. NEFA was unaffected. Significant falls in TAG only occurred in individuals with the GG variant of the 25444, 30294, -31118 or -33137 SNPs. The TAG-lowering effects may be via stimulation of CD36 activity in extrahepatic tissue in individuals with the GG variants of these SNPs.