The objective of this study was to determine if gender differences exist when using the Manning criteria for diagnosis of irritable bowel syndrome. In an outpatient setting, 61 women and 36 men with entry complaints of abdominal pain, altered bowel habits, or both underwent full evaluation by board-certified/eligible gastroenterologists who also systematically rated the presence or absence of the six Manning criteria. Irritable bowel syndrome was defined as the absence of an organic disease explanation for the entry complaints. This determination was made by two other board-certified gastroenterologists after patients had been in the study for 9 months. These raters were independent of the study and rated the transcripts of patients' clinic visits, all other available clinical data from this and other clinics, all laboratory data obtained during the 9-month study period, and the results of a 9-month telephone follow-up to patients and their physicians. Sixty-five percent of the study population had no organic disease explanation for the entry symptoms, thereby representing irritable bowel syndrome for this study. A similar proportion and type of organic disease and irritable bowel syndrome were experienced by men and women. For the total sample of 97 subjects, the correlation of the Manning criteria with irritable bowel syndrome was 0.22 (P less than 0.01). In the 61 women, correlation between the Manning criteria and irritable bowel syndrome was significant (r = 0.47; P less than 0.01). In the 36 men, however, the correlation was in the opposite direction, although it was not significant (r = -0.16). It was concluded that significant gender differences exist when using the Manning criteria for the diagnosis of irritable bowel syndrome and that the Manning criteria were not of diagnostic value in men.