The consumption of tomato products is associated with a reduced risk of cardiovascular disease and several cancers. It is hypothesized that lycopene, the major carotenoid in tomato products, may mediate this relationship. We designed a study to examine changes in plasma and buccal mucosal cell (BMC) lycopene concentrations in healthy adults consuming standard daily servings of processed tomato products: spaghetti sauce, tomato soup, or vegetable juice. Thirty-six healthy subjects consumed a lycopene-free diet for 2 wk and were then assigned to one of three (n = 12) intervention groups consuming daily, single servings of sauce (21 mg lycopene per (1/2) cup), soup (12 mg lycopene per 1 cup), or juice (17 mg lycopene per 8 oz) for 4 wk. Fasting blood and BMC samples were evaluated by high-performance liquid chromatography analysis for carotenoids and lycopene isomers. Total plasma lycopene concentrations (Mean +/- SEM) decreased from 1.05 +/- 0.07 to 0.54 +/- 0.05 micromol/l (49%, P < 0.0001) during the 2-wk washout period. Following intervention, plasma lycopene concentrations increased significantly for those consuming sauce, soup, and juice (compared with washout baseline) to 2.08 (192%, P < 0.0001), 0.91 (122%, P < 0.0001), and 0.99 (92%, P < 0.0001) micromol/l, respectively. Plasma isomer concentrations show a 61:39 ratio of cis:all-trans at the start of the study. During the 2-wk washout the decrease in plasma all-trans-lycopene was greater than that for pooled cis isomers (70:30 cis:trans ratio, P < 0.001). After 2 wk of dietary intervention isomer ratios returned to those observed at the start of the study. Total BMC lycopene concentrations did not significantly change during the brief washout. During the 4-wk intervention period, BMC total lycopene concentrations increased (P < 0.005) by 165, 42, and 48% nmol/mg protein for those consuming sauce, soup, and juice, respectively. This study demonstrates that plasma lycopene decreases by 50% after approximately 2 wk on a lycopene-free diet with a decrease in the ratio of all-trans compared with cis isomers. Single, daily servings of processed tomato products significantly increase blood and BMC lycopene for 2 wk. Additional studies of lycopene bioavailability, isomerization, metabolism, and bioactivity will provide greater insight into the potential health benefits suggested by epidemiological studies and laboratory investigations.