Postoperative changes in endocrinological status and serum chemistry during the 4 years after transsphenoidal surgery (ISS) in 25 dogs with Cushing's disease were investigated in a prospective study. In all 25 dogs. Cushing's disease was diagnosed from resected pituitary tissues as a corticotroph adenoma in the anterior lobe of the pituitary. Prior to TSS, all 25 clogs showed hypercortisolemia. After TSS, the ACTH stimulation test showed continued low serum cortisol concentrations in 21 dogs (84%). In addition, the serum thyroid stimulating hormone concentrations decreased sequentially, while the serum T4 concentrations tended to increase due to the postoperative hormone substitution therapy utilized to avoid secondary hypothyroidism. In recital to serum chemistry. alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total cholesterol are commonly increased in can Cushing's disease. In this study. ALP. ALT and total cholesterol were increased in 23 eases (92%), 19 cases (76%) and 20 cases (80%). respectively. However. postoperatively, these concentrations gradually decreased. The postoperative serum concentrations of ALP at I year, that of ALT at six months to 2 years and that of total cholesterol over the course of the 4 years decreased significantly compared with the concentrations before TSS. These results show that TSS is an effective treatment for canine Cushing's disease and for long-term improvement of hypercortisolemia. Moreover. TSS is effective in improvement or hypercortisolism, such as increased concentrations of serum ALP. ALT and total cholesterol.