The antifolate-type anticancer drug methotrexate (MTX) has for many years, in numerous laboratories, been a "workhorse" drug for conjugation with natural and synthetic macromolecular carriers for the purpose of enhancing bioavailability and lowering toxic side effects. In the project here described the polymer-drug conjugation strategy is utilized for the preparation of water-soluble polyaspartamide-methotrexate conjugates in which the drug is carrier-anchored through short spacers containing ester groups as biofissionable links. To this end, polyaspartamide carriers 1, poly-alpha,beta -D,L-N-(2-hydroxyethyl)aspartamide, and 2, poly-alpha,beta -D,L-N-[2-(2-hydroxyethoxy)ethyl]aspartamide, are treated with MTX in DMF solution in the presence of a carbodiimide coupling agent and 4-(dimethylamino)pyridine catalyst. The molar MTX/OH feed ratios, 0.28 and lower, are chosen in these coupling reactions so as to provide conjugates featuring drug-loading levels in the approximate range of 3-16 mol % MT) roughly corresponding to 6-28% by mass. The water-soluble product polymers are purified by aqueous dialysis, collected in the solid state by freeze-drying, and structurally characterized by H-1-NMR spectroscopy.