Because even after low doses of fructose and sorbitol, fructose-sorbitol malabsorption has been found in a high number of patients with the irritable bowel syndrome, an etiological role of fructose-sorbitol malabsorption in the irritable bowel syndrome has been suggested. However, these studies have been uncontrolled. Therefore, a controlled study of fructose-sorbitol malabsorption in the irritable bowel syndrome compared with healthy controls was performed. Seventy-three patients, 23 men and 50 women with a mean age 43.1 +/- 1.7 years (range, 18-66 years) with the irritable bowel syndrome were compared with 87 age- and sex-matched control subjects. Fructose-sorbitol malabsorption was determined by a breath-hydrogen test (Lactoscreen, Hoek Loos, Schiedam, The Netherlands) following an oral load of 25 g fructose and 5 g sorbitol after a 10-hour fast. Fructose-sorbitol malabsorption, as shown by an H2 peak of 20 ppm over basal values, was found in 22 (30.1%) of the patients and 35 (40.2%) of the control subjects. With a lower peak level of 10 ppm over basal values, these percentages were 45.2% and 57.5%, respectively. Also, the highest H2 peak values (15.2 +/- 2.3 ppm vs. 21.5 +/- 2.6 ppm), time to reach peak levels (110.7 +/- 5.4 min vs. 107.1 +/- 5.9 min), and area under the H2 curve (1310 +/- 219 ppm.min vs. 1812 +/- 255 ppm.min) did not discriminate between patients and controls. During the test, symptoms developed in 31 of 70 patients and in 3 of 85 control subjects (P less than 0.0001). Symptomatic patients did not differ from asymptomatic patients regarding the presence or absence of fructose-sorbitol malabsorption, H2 peak values, and area under the curve. No differences could be identified between male and female patients or controls. In conclusion, fructose-sorbitol malabsorption is frequently seen in patients with irritable bowel syndrome, but this is not different from observations in healthy volunteers. Therefore, fructose-sorbitol malabsorption does not seem to play an important role in the etiology of irritable bowel syndrome.