Lycopene (lyc) has emerged as a primary candidate for dietary interventions of prostate cancer; however, research regarding its absorption, tissue distribution, and metabolism is limited. Previously, we evaluated the biodistribution (3-168 h) of a single oral dose of 14C-lyc in rats prefed lyc for 30 d. The liver was the primary depot for lyc, and the 14C and 14C-polar products appeared in tissues as early as 3 h after dosing. In the current study, F344 rats (n = 48) were randomly assigned to 1 of 4 groups prefed either a control or lyc-enriched diet (0.25 g lyc/kg diet) for 30 d and killed at 5 or 24 h after receiving a single oral dose of 14C-lyc. The percentage of the 14C dose absorbed at 24 h was lower (5.5 +/- 0.5%) in lyc-prefed (LP) rats than in control-prefed (CP) rats (6.9 +/- 0.4%, P < 0.04). Hepatic total 14C and 14C-lyc in CP rats was greater than in LP rats at 24 h (P < 0.005). A portion of 14C was delivered to extrahepatic tissues as early as 5 h, irrespective of diet. Of the tissues analyzed, an increase in the percentage in 14C-polar products occurred between 5 and 24 h only in the prostate and seminal vesicles, suggesting increased accumulation of 14C-polar products in these tissues, irrespective of prior dietary treatment. These data suggest that lyc absorption, tissue uptake, and catabolism were affected by prefeeding and that lyc can be partially taken up by extrahepatic tissues from the postprandial triglyceride-rich fraction.