Lycopene, the predominant carotenoid in tomatoes, is hypothesized to mediate the health benefits of tomato products. We designed a study to examine the change in plasma lycopene and resistance of lipoproteins to ex vivo oxidative stress. Healthy individuals (n = 60; age >40 y; 30 men/30 women) consumed a lycopene-free diet for 1 wk and were subsequently randomized to receive 35 +/- 1, 23 +/- 1 or 25 +/- 1 mg lycopene/d from Campbell's Condensed Tomato Soup (CS), Campbell's Ready To Serve Tomato Soup (RTS) or V8 Vegetable Juice (V8), respectively, for 15 d. Total plasma lycopene concentrations decreased from 0.499 +/- 0.044 to 0.322 +/- 0.027 (35%, P < 0.0001) micro mol/L for the 60 participants during the 7-d washout period. After intervention, total lycopene concentrations increased for those consuming CS, RTS and V8 (compared with the washout period for each group) to 0.784 +/- 0.083 (123%, P < 0.0001), 0.545 +/- 0.061 (57%, P < 0.01) and 0.569 +/- 0.061 (112%, P < 0.0001) micro mol/L, respectively. The concentrations of all lycopene isomers decreased during the washout period. As a percentage of plasma total lycopene isomers for the 60 subjects, all-trans-lycopene decreased from 44.4 +/- 1.2 to 39.6 +/- 1.2 (P < 0.0001), whereas total cis-lycopene isomers increased from 55.6 +/- 1.2 to 60.4 +/- 1.2 (P < 0.0001) during the washout period, a shift that was reversed by consumption of tomato products for 15 d. The ex vivo lipoprotein oxidation lag period, used as a measure of antioxidant capacity, increased significantly from 64.7 +/- 2.4 min at the end of the washout period (all groups) to 70.1 +/- 4.0 (P < 0.05), 68.3 +/- 2.4 (P < 0.05) and 71.7 +/- 4.0 min (P < 0.01) after treatment for the CS, RTS and V8 groups, respectively. This study shows that lycopene concentrations and isomer patterns change rapidly with variation in dietary intake. In addition, 15 d of tomato product consumption significantly enhanced the protection of lipoproteins to ex vivo oxidative stress.