In this study, macromolecular drug carriers based on N-(2-hydroxypropyl)methacrylamide (pHPMA) were investigated for their uptake into the tumor cell lines AT-1 and Walker-256. A short and a longer polymer chain of structurally different pHPMA variants (homopolymers, random copolymers, block copolymers) were examined in detail. In preliminary experiments, it was shown that these differed in terms of biodistribution and tumor accumulation in both rat tumor models. Therefore, these two tumor models were characterized in vivo with respect to vessel density, pO2, extracellular pH and other parameters. In cell culture experiments, the impact of a hypoxic and acidotic environment on the uptake of polymers in both cell lines was determined. In addition, possible endocytosis pathways of the polymers were investigated by inhibitor studies and the impact of hypoxia and acidosis on these endocytosis pathways.