We evaluated the reliability of IgA and IgG antigliadin antibodies (AGA-A, AGA-G), antireticulin antibody (ARA), endomysial antibodies (EmA), and alpha 1-antitrypsin clearance (alpha 1-AT CL) in the detection of celiac sprue (CS) in 59 first-degree asymptomatic relatives of celiac patients who had duodenal biopsy. Twenty-four relatives who had normal results of screening tests were selected at random for biopsy; 35 relatives with at least one abnormal test result were biopsied. Eleven relatives were noted to have villous atrophy at biopsy; the diagnosis of celiac sprue was confirmed by histological improvement after gluten-free diet in six. AGA-G, alpha 1-AT CL, and EmA had sensitivities of 73%, 73%, and 64%, respectively, with very high levels of specificity. Sensitivity was improved by the combination of two serological markers (AGA-G + alpha 1-AT CL = 91%; AGA-G + EmA = 82%; EmA + ARA = 82%). Furthermore, combination of EmA and ARA has shown the best specificity and positive predictive value. AGA-G, alpha 1-AT CL, and EmA are reliable individual markers for the detection of asymptomatic celiac sprue. However, a combination of two of them, including ARA, was more sensitive than the individual tests.