Fish oils rich in (n-3) long-chain PUFA (LCPUFA) can reduce circulating triglycerides and raise HDL-cholesterol. Phytosterols have been shown to reduce total cholesterol and LDL-cholesterol in normocholesterolemic and hyperlipidemic populations. We investigated the combined effects of phytosterols and (n-3) LCPUFA on plasma lipid profile in hyperlipidemic individuals. This study was a 3-wk randomized, double-blind, placebo-controlled, 2 x 2 factorial trial in 4 parallel groups of 60 hyperlipidemic individuals. Subjects were randomized to receive either sunola oil or 1.4 g/d (n-3) LCPUFA capsules with or without 2 g phytosterols per day while maintaining their habitual diet. The combination of phytosterols and (n-3) LCPUFA reduced plasma total cholesterol by 13.3% (P = 0.001), which differed from (n-3) LCPUFA alone (P < 0.001). LDL-cholesterol concentrations followed the same pattern as that of plasma cholesterol with a 12.5% decrease (P = 0.002) in the combination group. The HDL-cholesterol concentration was increased by (n-3) LCPUFA (7.1%; P = 0.01) alone and in combination with phytosterols (8.6%; P = 0.04), whereas phytosterol treatment alone had no effect. Plasma triglyceride concentration was lowered by (n-3) LCPUFA (22.3%; P = 0.004) alone and in combination with phytosterols (25.9%; P = 0.005), whereas phytosterol treatment alone had no effect. In conclusion, the combined supplementation with phytosterols and (n-3) LCPUFA has both synergistic and complementary lipid-lowering effects in hyperlipidemic men and women.