Mice and rabbits readily form antibodies in response to injections of Erwinia carotovora L-asparaginase (ASNase), and show accelerated blood clearance of the enzyme following treatment. In mice, by a suitable choice of dose of ASNase and schedule of administration, the immunological response could be minimized. There was evidence of specific immunological tolerance, shown more readily in terms of blood clearance than of serum antibody titres. A proportion of mice was also made tolerant using cyclophosphamide (CY) together with ASNase. In rabbits, the immunogenicity of ASNase could not be reduced in general, either by the use of centrifuged, aggregate-free enzyme, or by the use of reportedly tolerogenic regimens of CY or 6-mercaptopurine.