Vertebrate retina is highly enriched in 22-carbon polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA, 22:6n-3), which is supplied by the plasma. To study the transport and uptake of 22:6n-3 into the retina, young Long Evans rats were fasted overnight and given an oral dose of palm oil containing [4,5-3H] 22:6n-3 and [9,10-3H] 18:1n-9 (oleic acid). At 1, 6, 12, 24, and 48 hr postgavage, blood, liver, retinal pigment epithelium (RPE) and retina were collected, and plasma lipoprotein fractions were obtained by density-gradient ultracentrifugation. The distribution of radioactivity among the different lipoproteins (dpm%) showed that both fatty acids were mainly associated with VLDL 1 hr after gavage. For 22:6n-3, the majority of radioactivity was associated with LDL at 6 hr postgavage. By 12 hr post administration, the majority of radioactivity was in HDL2 which retained around 40% until the 48-hr time point. For 18:1n-9, a different profile was observed. By 6 hr postgavage, approximately 30% of the radioactivity was found in HDL2, but the percentage of radioactivity decreased to approximately 20% thereafter. The half-life of 22:6n-3 was significantly longer than for 18:1n-9 (P < 0.0005) in plasma, liver, and the lipoprotein fractions. The specific activities of 22:6n-3 and 18:1n-9 in the plasma continuously declined from 1 hr to 48 hr postgavage, while liver showed a peak of specific activity at 6 hr, then gradually declined.(ABSTRACT TRUNCATED AT 250 WORDS)