The authors have analyzed several endocrine and metabolic parameters in polyoma large T transgenic mice (PyLT-1) that develop adrenocorticotropic hormone (ACTH)-immunoreactive pituitary tumors and in nontransgenic mice with tumor transplants. All clinically ill PyLT-1 mice (13 to 16 months of age) had pituitary macroadenomas and elevated plasma ACTH levels. Compared to PyLT-1 transgenic mice, the ACTH plasma concentrations in immunocompetent mice with transplant tumors were markedly raised. In these animals, a secondary effect of hypercorticotropism was documented by a moderate hyperglycemia. Furthermore, mice with transplant tumors had a pathological weight increase from the time the tumor was palpable. The present study supports and extends the authors' previous morphological documentation of the similarity between the ACTH-producing tumors in this mouse model and human Cushing's disease.