When 10 diabetic (five insulin-dependent) subjects with reasonable glycemic control were randomized from their usual (U) diet (about 30 g fiber/day) between two different but isocaloric high fiber diets, each sequentially over 6 wk [HF (55 g fiber/day) and HFS (55 g fiber/day with sucrose taken as 15 g three times daily, with meals)], plasma acetate (mmol/L) increased by 35% on both high fiber diets from 0.21 +/- 0.06 (SD) to 0.28 +/- 0.10 (HF) and 0.30 +/- 0.10 (HFS) (both p less than 0.01). This was higher than the random weekly variation in plasma acetate levels of 11% in six other glycemically stable diabetic patients. When the acetate value was expressed as acetate/glucose, i.e., relative to the fasting glucose level (since fasting levels of acetate and glucose consistently positively correlate), the increase was about 80%. Fasting plasma non-esterified fatty acid (NEFA) levels fell during the high fiber diets and correlated negatively with the fasting acetate level (rs -0.51, p less than 0.005). The fall in NEFA and rise in acetate levels appeared greatest with the sucrose-supplemented meals. These results suggest increased exogenous contribution to the plasma acetate level from increased colonic fermentation of dietary fiber and raise the possibility of using such measurements in the assessment of compliance to high fiber diets. The fall in NEFA levels associated with raised plasma acetate levels may contribute to the beneficial effects on glycemic control observed with the high fiber diets.