To determine whether chronic high-fructose feeding causes insulin resistance and hypertension in normal dogs, we fed 10 male dogs a normosodic diet containing 60% of the calories as fructose for 20 to 28 days; a control group of 8 dogs was fed a similar diet containing dextrose instead of fructose. In the fructose-fed group, (1) fasting triglyceridemia increased from 35.3 +/- 0.63 to 91.9 +/- 11.55 mg/dL after 25 days (P < .001); (2) fasting insulinemia increased from 19.0 +/- 1.9 to 58.9 +/- 7.22 microU/mL after 25 days (P < .001); (3) insulin resistance, which was estimated by steady-state glycemia during an insulin suppression test, increased from 105.8 +/- 21.5 to 187.8 +/- 32.6 mg/dL after 15 days (P < .001), whereas steady-state insulinemia did not change; (4) mean arterial pressure increased from 100.4 +/- 1.6 to 122.6 +/- 2.3 mm Hg after 28 days (P < .01); and (5) cumulative sodium balance was increased on days 7 through 11 (111.60 +/- 4.44 mEq on day 8, P < .01), returning to normal for the rest of the experiment. All these parameters were similar between the fructose-fed and dextrose-fed groups before the diets were started and remained constant in the dextrose-fed group. Neither group showed any change in body weight, fasting plasma glucose, atrial natriuretic factor, or endothelin-1 levels. We conclude that chronic high-fructose feeding elicits hypertriglyceridemia, insulin resistance, hyperinsulinemia, hypertension, and a transient sodium retention in dogs without fostering fasting hyperglycemia or weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)