Soluble macromolecular conjugates for the controlled delivery of the strongly hydrophobic antitumor drug adriamycin (ADR) were prepared. The association behaviour of two types of these amphiphilic conjugates consisting of ADR bound to poly(L-glutamic acid) (PGA) in aqueous solution was investigated using absorbance and fluorescence spectroscopy as well as GPC and lowangle laser light scattering (LALLS) measurements. ADR was bound via the aminoribosyl moiety either directly with PGA side-chain groups or via oligopeptide spacer groups. UV/VIS, GPC and LALLS data showed that in buffer solution both ADR conjugates associate intermolecularly. The data of the directly bound ADR conjugates are consistent with the presence of multimers of different degrees of association in equilibrium with single polymer chains. In contrast, spacer-containing ADR conjugates associate to give stable uniform multimers. UV/VIS and fluorescence spectroscopy performed at very low conjugate concentration show that polymer-bound ADR residues associate intramolecularly as well. The degree of intra- and intermolecular association of the conjugate-bound ADR molecules depends on the type of conjugate, ADR load and conjugate concentration as well as on ionic strength of the solvent, the presence of organic cosolvents and temperature. The data indicate that hydrophobic domains in spacer-containing conjugates are more stable compared with directly bound conjugates, probably due to enhanced flexibility and the presence of hydrophobic leucine residues. It is concluded that spacer-containing conjugates of ADR may have a potential for effective drug delivery under in vivo conditions due to their solution properties in addition to the biodegradability of the drug-polymer bond.