Glomerulonephritis has been associated with exogenous glucocorticoid administration and spontaneous hyperadrenocorticism in the dog. The purpose of this study was to determine the effects of long-term glucocorticoid therapy on urine protein:creatinine ratios (UP/Cs) and renal morphology. Nine young-adult male dogs were determined to be healthy and have normal renal function as assessed by physical examination, CBC, serum biochemistry analysis, Knott's test for Dirofilaria immitis, urinalysis, urine culture, urine protein electrophoresis, endogenous creatinine clearance, 24-hour urinary protein excretion, and UP/C. Prednisone was administered to each dog at a dosage of 2.2 mg/kg PO bid for 42 days. Urinalysis and UP/C were performed on days 0, 7, 14, 21, 28, and 42 of treatment. Mean UP/C on day 0 was 0.29 +/- 0.10. Mean UP/C increased progressively to a maximum of 1.27 +/- 1.02 on day 28. Mean UP/C on day 42 decreased slightly (0.92 +/- 0.56) but remained significantly increased above baseline. The most consistent renal light microscopic finding on necropsy examination was generalized hypercellular glomerular tufts, suggestive of mesangial cell proliferation. Four dogs also had occasional adhesions of glomerular tufts to Bowman's capsule, accompanied by thickening of the capsule. Direct immunofluorescence for immunoglobulin deposition was negative in all dogs. Electron microscopy, evaluated in 7 dogs, was characterized by occasional mild segmental thickening of basement membranes, fusion of visceral cell foot processes, and glomerular adhesions. The results of this study indicate that long-term administration of glucocorticoids results in significant proteinuria and glomerular changes in the dog.