The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% greater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-beta1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.