Fish consumption is associated with reduced cardiovascular mortality, and elevated myocardial long-chain n-3 polyunsaturated FA (PUFA) content is implicated in this cardioprotection. This study examined the dose and time responses for incorporation of n-3 PUFA into cellular membranes in rats fed fish oil (FO)-containing diets. For the time course study, rats were fed a 10% FO diet for periods ranging from 0 to 42 d, after which myocardial and erythrocyte membrane fatty acid composition was determined. For the dose response study, rats (n = 3) were fed 0, 1.25, 2.5, 5, or 10% FO for 4 wk, with myocardial, erythrocyte, and skeletal muscle membrane FA determined. Myocardial DHA (22:6n-3) levels doubled in 2 d, stabilizing at levels approximately 200% higher than control after 28 d feeding with 10% FO. By comparison, DHA levels doubled after 4 wk of 1.25% FO feeding. In myocardium and skeletal muscle, EPA (20:5n-3) levels remained low, but in erythrocytes EPA levels reached 50% of DHA levels. The n-3 PUFA were incorporated at the expense of n-6 PUFA in myocardium and skeletal muscle, whereas erythrocytes maintained arachidonic acid levels, and total n-3 PUFA incorporation was lower. This study shows that low doses of FO produce marked changes in myocardial DHA levels; maximal incorporation takes up to 28 d to occur; and while erythrocytes are a good indicator of tissue n-3 incorporation in stable diets, they vary greatly in their time course and pattern of incorporation.