Epidemiologic and laboratory studies suggest a possible role for tomato products, a rich source of the carotenoid lycopene, in the prevention of certain cancers and cardiovascular disease. Lycopene is consumed primarily as the all-trans-isomer, but the majority of lycopene in blood and tissue exists as a variety of cis-isomers. Specific isomers may be involved in different biological reactions, and patterns of isomers may provide insight into the risk or pathogenesis of disease processes. Total lycopene concentration and the concentrations of the cis- and trans-lycopene isomers were measured by HPLC in plasma samples taken 3-4 y apart from 144 mostly nonsmoking male participants in the Health Professionals Follow-up Study. Correlations between plasma concentrations determined 3-4 y apart ranged from 0.55 (all-trans-isomer) to 0.70 (cis-isomer 5 -cis) (P < 0.001). For total lycopene, the correlation was 0.63 (P < 0.001). Total cis-lycopene contributed approximately 67% of total lycopene (range 50-79%). At each time point, the various lycopene isomer concentrations were highly correlated with one another with Spearman correlation coefficients ranging from 0.90 to 0.99 (P < 0.001). Plasma concentrations of total lycopene and its most abundant isomers in samples taken 3-4 y apart were strongly correlated, indicating that dietary patterns and metabolic processes defining lycopene concentrations are stable over time. Because the patterns of lycopene isomers showed limited between-person variability, our results suggest that measuring specific lycopene isomers in epidemiologic studies may not provide additional information beyond that provided by total lycopene concentration. Single plasma samples quantitating plasma lycopene are a valid predictor of long-term exposure for epidemiologic studies.