The diagnostic value of 1-14C-lactose breath test was compared with the standard lactose tolerance test and lactase assay in jejunal biopsies in 16 control subjects, 14 patients with lactase deficiency (LD) proven by lactase assay and 20 patients with irritable bowel syndrome (IBS). 14CO2 specific activity in the 2-hr breath collection after administration of 1-14C-lactose (5 muCi) provided a satisfactory separation between the control and LD group. Values were 7.0 +/- 2.0% dose administered/mmoles 14CO2 X 10(-3) (mean +/- SD) in the control group versus 2.1 +/- 1.5 in LD (P less than 0.001) versus 4.9 +/- 2.3 in IBS (P less than 0.01). 1-14C-lactose breath test was superior to standard lactose tolerance test in specificity (P less than 0.05) and provided a satisfactory correlation between 14C-lactose absorption and lactase assay (r = 0.77). The prevalence of LD in IBS was 40% by the breath test and 35% by lactase assay, suggesting that lactose malabsorption may play a role in the symptoms in the population of some patients with IBS. It appears that 1-14C-lactose breath test is a sensitive, specific and accurate method for the diagnosis of LD in clinical practice and suitable for large scale epidemiological surveys.