Conjugates of curcumin to two differently sized poly(ethylene glycol) molecules were synthesized in an attempt to overcome the low aqueous solubility of this natural product with cytotoxic activity against some human cancer cell lines. The soluble conjugates exhibited enhanced cytotoxicity as compared to that of the parent drug. Synthesis, analyses of the rate of drug release, and cytotoxicity studies are herein reported. The water-soluble conjugates may provide information useful for the development of injectable curcumin conjugates. © 2007 American Chemical Society.