Background: Bioavailability studies with lycopene have focused on natural sources. A synthetic source has recently become available. Aim of the study: To determine the relative bioavailabilities of synthetic and tomato-based lycopene in free living volunteers in a single-blind, randomized, placebo-controlled, parallel trial. Methods: Three groups (n = 12/group) of healthy, normolipemic male and female subjects with a mean baseline serum lycopene concentration of 0.36 μmol/L took a dose of 15 mg/day total lycopene for 28 days from either Lycovit 10 % (beadlets, BASF, Germany) or Lyc-O-Mato (beads, LycoRed Natural Products, Israel) or a placebo (without lycopene) together with the main meal. The increase in serum lycopene from baseline was used as the parameter of bioavailability. Results: Synthetic and tomato-lycopene resulted in significant increases above baseline of serum total lycopene by 0.58 and 0.57 μmol/L, trans-lycopene by 0.34 and 0.41 μmol/L, and total-cis-lycopene by 0.24 and 0.16 μmol/L, whereas no significant changes were found in the placebo treatment. The mean serum total lycopene response to synthetic and natural lycopene was not significantly different. Neither lycopene source affected the other serum carotenoids, viz. α-carotene, β-carotene, β-cryptoxanthin, zeaxanthin and lutein. Conclusion: We conclude that synthetic and natural lycopene are equivalent sources of lycopene and that there is no interaction with other circulating carotenoids.