Background:The purpose of this study was to investigate whether the increased intestinal permeability (IP) seen in patients with cystic fibrosis (CF) is correlated with the basic defect, as revealed by the patient's genotype, and/or whether the intestinal disturbance reflects secondary abnormalities such as essential fatty acid deficiency.Methods:Nineteen CF patients were compared with nine age- and sex- matched healthy controls. IP was evaluated by studying urinary excretion for 5 hours after a test meal containing lactulose, L-rhamnose and xylose in water. Urine was analyzed for carbohydrates, and blood samples were taken for determination of the fatty acid pattern of serum phospholipids. The CF patients were grouped according to genotype: homozygous for ΔF508, heterozygous for ΔF508, or unidentified.Results:Patients who were homozygous (n = 9) or heterzygous (n = 6) for ΔF508 had significantly higher lactulose/L-rhamnose excretion ratios (mean(range) values of 0.08(0.05-0.13) and 0.09(0.03-0.13), respectively) than patients (n = 4) with unidentified genotypes [0.03(0.02-0.05); p = 0.005] or healthy controls [0.02(0.003-0.06); p = 0.002]. CF patients with EFAD (n = 6) did not differ from those with a normal pattern of serum phospholipid fatty acids, the lactulose/L-rhamnose excretion ratio being 0.08(0.02-0.13) and 0.07(0.03-0.12), respectively.Conclusions:These data show that the IP in CF was related to patient genotype; those homozygozous or heterozygous for ΔF508 having a significantly increased IP compared with patients with unidentified genotypes, who had IP values within the normal range.