Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to inhibit neutrophil and monocyte chemotaxis in healthy subjects and, with respect to neutrophils, also in various patient groups. We studied the effect of dietary supplementation with n-3 PUFAs on monocyte and neutrophil chemotaxis in patients with hyperlipidemia. Chemotaxis was investigated with the under-agarose assay, using autologous serum and N-formyl-methionyl-leucyl-phenylalanine as chemoattractants. The patients were examined before and after 6 weeks of supplementation with 6 g n-3 PUFAs daily. Monocyte chemotaxis was reduced after n-3 PUFA supplementation in type IIa patients but was unaffected in patients with type IV hyperlipidemia. Furthermore, monocyte chemotaxis was increased in untreated type IIa patients compared with normocholesterolemic controls. We also studied the dose-response effects of n-3 PUFAs on monocyte and neutrophil chemotaxis in healthy men given 1.3, 4, and 9 g n-3 PUFAs daily for 6-week periods. Monocyte and neutrophil chemotaxis was reduced after n-3 PUFA supplements in a dose-dependent fashion, with the majority of the effect observed after the low dose. These results lend support to the notion of an antiatherosclerotic effect of n-3 PUFAs and may provide an explanation for the hitherto-unexplained effect of low doses of n-3 PUFAs in coronary heart disease.