There is concern that dietary factors can modulate the insulin-like growth factor (IGF) system. The aim of this work was to evaluate the effect of a tomato drink intervention providing small amounts of lycopene and other carotenoids on serum levels of IGF-1. Twenty healthy young subjects participated in a repeated measure double-blind, cross-over design. Subjects consumed 250 ml of a tomato drink or a placebo drink for 26 days separated by 26 days wash-out. The tomato drink intake increased plasma lycopene, phytoene, phytofluene, and beta-carotene concentrations by 0.22, 0.12, 0.13, and 0.18 micromol/L, respectively (P < 0.05). No significant effect of the tomato drink intake on IGF-1 levels was observed. However, changes in lycopene before and after each experimental period were inversely and significantly correlated with those of IGF-1 (r = -0.33, P < 0.05, N = 20). No correlation was found with the other carotenoids. A significant reduction of IGF-1 serum level (-5.7%) was observed in subjects (n = 11) with the highest plasma lycopene response but also IGF-1 levels following the tomato drink intake (P < 0.05). No effect was evident after the placebo treatment. The results suggest that further exploration of the role of tomato lycopene on IGF-1 modulation both on healthy and on subjects at risk is necessary.