This study examined patterns of changes in plasma fatty acids and carotenoids when women were asked to follow a novel, Greek-Mediterranean exchange list diet. A total of 69 healthy, nonobese women ages 25 to 59 years were randomized either to continue their own usual diet or to follow a modified Mediterranean diet for 6 months. There were no significant changes in blood lipids, triacylglycerol, insulin, glucose, or C-reactive protein. Mean plasma carotenoids increased by 55%, which is consistent with a large increase in fruit and vegetable consumption. Likewise, changes in fat intakes were reflected in blood fatty acids, with a 25% increase in mean plasma monounsaturated fatty acids. Principal component analysis was conducted to examine the sources of interindividual variation for changes in carotenoid and fatty acid levels. Changes in the Mediterranean diet were clustered together in 4 components that accounted for 78% of the variance in plasma levels. Increases in plasma lutein, alpha-carotene, and beta-carotene clustered together in a "vegetable" pattern, and increases in carotenoids found in fruit, beta-cryptoxanthin and zeaxanthin also clustered together but accounted for less of the variance. Increases in plasma monounsaturated fatty acids were clustered with a decrease in plasma polyunsaturated fatty acids, consistent with substitution in the type of oils consumed. The only association of fatty acid levels with carotenoids was that of lycopene, which clustered together with an increase in saturated fatty acids. The changes in blood levels indicate the exchange list diet was effective for targeting Mediterranean nutrient intakes using foods available in the United States.