The effect of diet on the metabolism of eicosapentaenoic acid (EPA) and gammalinolenic acid (GLA) was investigated in two groups of African Green Vervet monkeys fed either a Western atherogenic diet (WAD; %E fat 43.5%; P:S 0.3; n=10) or a high carbohydrate diet (HCD; %E fat 20.5%; P:S 3.4; n=10). Vervets within each dietary treatment were supplemented with 300 mg/day with either an EPA concentrate (50% as free fatty acid, n=5) or a GLA concentrate (70% as free fatty acid, n=5) for 24 weeks, increasing the dose every 6 weeks to a maximum of 2400 mg/kg/day. Vervets in the WAD-Group consumed 433.7 mg/kg/day of EPA and those in the HCD-Group 318.2 mg/kg/day of EPA, whereas 421 mg/kg/day of GLA was consumed in the WAD Group and 340 mg/kg/day in the HCD Group during the last 6 weeks (week 18-24) of the supplementation period. The rate of disappearance of EPA and GLA from plasma and erythrocyte memebrane (EMB) phospholipids were estimated for the two diets after supplementation was stopped. The half-lives (t(1/2)) of EPA in EMB phosphatidylcholine (PC) were estimated to be 34.6 days (WAD) and 22.6 days (HCD), compared to 43.5 days (WAD) and 31.3 days (HCD) in EMB phosphatidylethanolamine (PE). In plasma cholesteryl ester (CE) t(1/2) was 23.5 days (WAD) compared to 14.1 days (HCD), and in plasma triacylglycerol (TAG) 17.4 days (WAD) compared to 9.4 days (HCD). Although accurate estimation of the GLA t(1/2) was difficult to assess due to the low tissue levels (probably due to rapid conversion to DGLA), the disappearance rates of GLA from EMB and plasma also suggested a faster metabolic rate in those animals consuming a HCD compared to a WAD. EPA also disappeared faster from EMB PC than from EMB PE. Disappearance of EPA from plasma TAG was also faster than from plasma CE, probably reflecting their relative turnover and metabolic rates. During supplementation, EPA substituted linoleic acid (C18:2 n-6), arachidonic acid (C20:4 n-6), and GLA (C18:3 n-6). This was reversed when supplementation was stopped. Plasma total cholesterol (TC) levels decreased by 17.06 +/- 17.67% in animals consuming the HCD with EPA as supplement, whereas in those consuming the WAD, plasma TC levels increased with 21.78 +/- 28.23% during the supplementation period. The delay of EPA and GLA disappearance from EMB and plasma in animals consuming a WAD, strongly suggests that metabolism of EPA and GLA is modulated by diet. Such a modulation could cause an accumulation of plasma TC levels that could explain the contradictory results reported by previous studies.