In a previous study we observed a clear difference in lactose intolerance symptoms after a 25-g lactose load in two groups of persons with lactase nonpersistence and similar small intestinal lactase activity. From this observation we hypothesized a colon resistance factor. To identify this factor, the microbial composition of fecal samples of the two lactose intolerant groups (one with mild symptoms, n = 16, and one with diarrhea-predominant symptoms, n = 11) was compared using the fluorescent in situ hybridization technique. Large interindividual differences were found in the numbers of total bacteria and main groups of bacteria (CV: 0.65 and 0.64-0.82 respectively). The bacterial numbers were not significantly different between the two groups. A significant negative correlation, however, was found between the individual symptom scores of the intolerant persons and the numbers of total hybridizable bacteria (r(s) = -0.42, P = 0.03). The results suggest that an increased number of bacteria might contribute--by means of a higher fermentative capacity--to the reduction of lactose intolerance symptoms.