Oral lactose-ureide is resistant to human digestive enzymes, but is fermented by the colonic microflora. Nine normal adults consuming a diet which provided 36 g of protein/day were given oral doses of lactose-[(13)C]ureide and lactose-[(15)N,(15)N]ureide. The appearance on breath of (13)CO(2) derived from lactose-[(13)C]ureide was followed for 48 h. The fate of (15)N derived from lactose-[(15)N, (15)N]ureide was determined by measuring the recovery of (15)N in stools and urine in various forms. About 80% of the label given as lactose-[(13)C]ureide was recovered on the breath, and about 80% of label given as lactose-[(15)N,(15)N]ureide was not recovered in stool, indicating that 80% of the dose was completely fermented. At least 5% of the labelled urea was absorbed and excreted as the intact molecule. Of the (15)N derived from lactose-[(15)N, (15)N]ureide and available for further metabolic interaction, 67% was retained and 33% was excreted in urine. The time taken for [(15)N,(15)N]urea to appear in urine was similar for all subjects, but the appearance of either (13)CO(2) on the breath or [(15)N, (14)N]urea in urine varied. It is concluded that the hydrolysis of the sugar-urea bond may reflect oro-caecal transit time, but that other factors related to colonic bacterial metabolism determine the duration and extent of hydrolysis of urea by urease enzymes. Lactose-ureide can be used to probe the metabolic activity of the colonic microflora in normal individuals.