Polymeric conjugates of L-asparaginase and an excess of homologous albumin were compared with free L-asparaginase for antitumor activity using a mouse model 6C3HED lymphosarcoma and a human pancreatic tumor cell line, PANC-1. The asparaginase-albumin polymer is more resistant to proteolytic degradation compared to equivalent amounts of free enzyme and is more effective as an antitumor agent in prolonging survival of C3H/HeJ mice receiving 6C3HED lymphosarcoma. In terms of antitumor activity, the enzyme is approximately 20 times more effective, compared to free enzyme, when given in polymeric form with albumin. Similarly, the polymeric form of L-asparaginase is more effective in inhibiting cell growth of human pancreatic tumor cells grown in tissue culture. The increased effectiveness of the polymeric form of L-asparaginase is probably related to its resistance to biodegradation. The use of cell surface-specific monoclonal antibodies to target the polymer to tumor cells is also demonstrated.