Starlike HPMA copolymers were synthesized by conjugating semitelechelic poly[N-(2-hydroxypropyl)-methacrylamide] macromolecules (ST-PHPMA, arm) with PAMAM dendrimers (core: G2, G3, G4). ST-PHPMA was synthesized by chain transfer free radical polymerization, and the terminal -COOH was activated with N-hydroxysuccinimide. Doxorubicin (DOX) was introduced into the starlike HPMA copolymer to evaluate its potential as a drug delivery system. The polymers were characterized with SEC, NMR, and UV. Cytotoxicity of the DOX containing starlike HPMA copolymer was determined on an A2780 human ovarian carcinoma cell line and compared with DOX-containing linear HPMA copolymers. The rate of in vitro DOX release from polymer-DOX conjugates in the presence of cathepsin B (CP-B, lysosomal cysteine proteinase) was determined and correlated with cytotoxicity results.