Purpose: The purpose of this Phase II randomized-controlled trial was to evaluate the safety and effect of administering several doses of lycopene to men with clinically localized prostate cancer, on intermediate endpoint biomarkers implicated in prostate carcinogenesis. Methods: Forty- ve eligible men with clinically localized prostate cancer were supplemented with 15, 30 or 45 mg of lycopene or no supplement from biopsy to prostatectomy. Compliance to study agent, toxicity, changes in plasma lycopene, serum steroid hormones, PSA and tissue Ki-67 were analyzed from baseline to completion of intervention. Results: Forty-two of forty- ve ve subjects completed the intervention for approximately 30 days from the time of biopsy until prostatectomy. Plasma lycopene increased from baseline to post treatment in all treatment groups with greatest increase observed in the 45 mg lycopene-supplemented arm compared to the control arm without producing any toxicity. Overall, subjects with prostate cancer had lower baseline levels of plasma lycopene similar to those observed in previous studies in men with prostate cancer. Serum free testosterone decreased with 30 mg lycopene supplementation and total estradiol increased signi cantly with 30 mg and 45 mg supplementation from baseline to end of treatment, with no signi cant increases in serum PSA or tissue Ki-67. These changes were not signi cant compared to the control arm for this sample size and duration of intervention. Conclusions: Although antioxidant properties of lycopene have been hypothesized to be primarily responsible for its bene cial effects, our study suggests that other mechanisms mediated by steroid hormones may also be involved.