Oxidative stress is recognized as one of the major contributors of increased risk of cancer. Many recent population studies have established a close link between dietary intake of tomatoes, a major source of the carotenoid antioxidant lycopene, and lowered risk of cancer. A study was conducted on 19 healthy human subjects to evaluate the uptake and in vivo antioxidant properties of lycopene, using a randomized, crossover design. Dietary lycopene was provided by tomato juice, spaghetti sauce, and tomato oleoresin for a period of one week each. Blood samples were collected at the end of each treatment. Serum lycopene was extracted and measured by high-performance liquid chromatography using an absorbance detector. Serum thiobarbituric acid-reactive substances, protein thiols, and 8-oxodeoxyguanosine contents of lymphocyte DNA were assayed to measure lipid, protein, and DNA oxidation. Lycopene was the major carotenoid present in the serum. Dietary supplementation of lycopene resulted in a significant increase in serum lycopene level and diminished amounts of serum thiobarbituric acid-reactive substances. Although not statistically significant, a tendency of lowered protein and DNA oxidation was observed. There was also indication that the lycopene levels increased in a dose-dependent manner in the case of spaghetti sauce and tomato oleoresin. These results indicate that lycopene is readily absorbed from tomato products and may act as an in vivo antioxidant. It may, therefore, play an important role in the prevention of cancer.