Insulin-like growth factors (IGF-I and IGF-II) have significant homology for insulin, and exhibit a high affinity for a family of binding proteins (IGFBPs). So far, six binding proteins (IGFBP 1-6) have been cloned and sequenced. The various IGFBPs share a common structure in that they contain similar N- and C- terminal cysteine domains separated by a less conserved domain. IGFBP-3 is the major binding protein in human serum, forming a 150-kDa complex with an acid labile subunit (ALS) and IGF. IGFBPs in the interstitial fluid are thought to regulate the bioavailability of locally secreted IGFs to their target cells and to modulate the biological effects of the IGFs by altering their interaction with the IGF receptor. Proteolysis of IGFBP-3 occurs in vivo and in several cell lines by serine protease. Earlier studies created two major IGFBP-3 fragments. The larger fragment proved to have weak affinity for IGF-I and weak inhibiting effect on IGF I mitogenic activity. The smaller fragment proved to be a potent growth inhibitor. The fragments were isolated by HPLC and partially sequenced. The research on the effects of IGFBP-3 fragments was significantly advanced by a recent development of IGFBP-3 fragments in the baculovirus system. Our initial studies with breast cancer cells (MCF-7) and prostate cancer cells (PC-3) have shown a pronounced growth inhibitory effects in those two cell lines (~60%). An apoptotic mechanism of the cell death is suspected.