OCI-5 encodes the rat homologue of glypican-3, a membrane-bound heparan sulfate proteoglycan that is mutated in the Simpson-Golabi-Behmel overgrowth syndrome. OCI-5 and glypican-3 are 95% identical. It has been recently suggested that glypican-3 interacts with insulin-like growth factor-2 (IGF-2) and that this interaction regulates IGF-I activity. We report here that we have transfected OCI-5 into two different cell lines, and we have not been able to detect an interaction between the OCI-5 proteoglycan produced by the transfected cells and IGF-2. On the other hand, we have found that OCI-5 interacts with FGF-S, as has already been shown for glypican-1. This interaction is mediated by the heparan sulfate chains of OCI-5 because it can be inhibited by heparin or by heparitinase.