During clinical trials utilizing the cancer chemotherapeutic enzyme L-asparaginase, hyperglycemia associated with low levels of serum immuno-reactive insulin have been observed in previously nondiabetic individuals. While the hyperglycemia usually abates following cessation of L-asparaginase therapy an abnormally low insulin response to glucose challenge may persist. Therefore, it has been suggested that L-asparaginase inhibits insulin biosynthesis perhaps through it's action of markedly decreasing serum L-asparagine levels. Since there is no published data regarding the effect of L-asparaginase on insulin biosynthesis and little pertainingto insulin release, it would be important to define the mechanism of the effect of this drug on the pancreatic beta cell. L-asparaginase, an enzyme, might effect insulin secretion and/or biosynthesis in a manner not previously recognized and would therefore be an important new tool with which to study beta cell function. Information regarding this effect would also allow one to devise various therapeutic regimes so that this diabetogenic toxicity of L-asparaginase could be mitigated without interfering with its therapeutic effectiveness. Therefore, the objectives of this study are to induce hyperglycemia with L-asparaginase in the rabbit and then determine whether this abnormality in glucose control is related to inhibition of insulin biosynthesis, inhibition of insulin release or to a combination of the two mechanisms. This will define the mechanism of L-asparaginase hyperglycemia and permit the development of methods for mitigating this toxicity.