Objective: High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of cardiovascular risk. We hypothesised that n-3 fatty acids reduce underlying inflammatory processes and consequently CRP concentrations in healthy middle-aged subjects. Design: Placebo-controlled, double-blind study. Subjects: A total of 43 men and 41 postmenopausal women aged 50 - 70 y. Before and after intervention, we measured serum CRP concentrations with an enzyme immunoassay. Interventions: Capsules with either 3.5 g/day fish oil ( 1.5 g/day n-3 fatty acids) or placebo for 12 weeks. Results: The median CRP change in the fish oil group did not significantly differ from that in the placebo group (0.01 vs - 0.17 mg/l, P = 0.057). Conclusion: The currently available data - including ours - do not support that beneficial effects on CRP are involved in a mechanism explaining the protective effect on heart disease risk of n-3 fatty acids as present in fish. Sponsorship: Wageningen Centre for Food Sciences.