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Glomerulonephritis (GN) is a leading cause of chronic renal failure in dogs. However, little is known about the efficacy of available treatment options for GN in this species. The purpose of this study was to determine the effects of cyclosporine (Cy) administration on the outcome of naturally occurring GN in dogs. Thirteen dogs from 4 institutions were included in the study. Randomization of dogs into placeboversus Cy-treated groups was stratified according to initial morphological diagnosis and contributing institution. Seven and 6 dogs were assigned to be given placebo or Cy, respectively. The initial Cy dose of 10 mg/kg every 24 hours was adjusted to maintain 24-hour trough, whole blood Cy concentrations between 250 and 400 ng/mL. There were no statistically significant differences between placebo-and Cy-treated groups with respect to serum total protein, albumin, urea nitrogen and creatinine, and plasma protein concentrations; platelet count; urine protein-creatinine ratio; endogenous creatinine clearance; 24-hour urine protein concentrations; or 24-hour urine protein—endogenous creatinine clearance ratio. However, PCV was significantly lower in the Cy-treated group. Decreased appetite, diarrhea, vomiting, weight loss, involuntary shaking, and thrombocytopenia were noted in both treatment groups; however, clinical signs in Cy-treated dogs subjectively were more severe. One Cy-treated dog developed gingival hyperplasia. After entry into the study, the median survival times for placebo-and Cy-treated dogs were 16 and 11 months, respectively. Considering the expense and the frequency of adverse effects related to Cy administration, the use of Cy in the treatment of dogs with GN does not seem warranted.