Oleyl alcohol was complexed with new amphiphilic polyvinylalcohol derivatives with the aim of increasing its aqueous solubility, thus improving bioavailability and favoring its antitumor activity. Water-soluble amphiphilic polymers were prepared by polyvinyl alcohol (PVA) substitution with oleyl chains through a succinyl spacer at 2% and 3% substitution degree. The complexes were obtained by spray-drying hydroalcoholic solutions of the substituted polymers and free oleyl alcohol at different weight ratios (3:1; 5:1; 10:1 w/w). The main physicochemical characteristics of the complexes were analyzed and correlated to the cytotoxic activity of oleyl alcohol toward tumor cell lines. The complexes strongly increased the aqueous solubility of oleyl alcohol and provided oleyl alcohol release in the presence of extractive conditions (simulating in vivo absorption). The complexes obtained by 10:1 polymer:fatty alcohol weight ratio offered higher release rates than the 5:1 and 3:1 ratios, respectively. Complexation also increased oleyl alcohol cytotoxicity toward tumor cells due to increased availability of the active molecule in the aqueous phase. Pure polymers were found to be biocompatible and no toxic effect was detected up to the highest concentration used in the present study (500 mu g/ml). The complexation of oleyl alcohol with the polymers analyzed here efficiently increased the availability of the fatty alcohol in aqueous environment. The enhanced cytotoxicity toward tumor cells of the complexed oleyl alcohol and the polymer biocompatibility make these amphiphilic PVA derivatives interesting candidates for soluble pharmaceutical formulations containing hydrophobic drugs whose therapeutic potential is often underestimated due to unsuitable levels of their aqueous solubilization.