HE DISCOVERY by Dicke and his co-workers [ir] that dietary gluten exerts a deleterious effect in patients with nontropical spruet proved to hold in itself, as Rich [2] has called the answer to each scientific question, “. . . the germ of a swarm of new questions.” Many inquiries have since arisen regarding the nature of this noxious effect. Particular stimulant of this interest is the probability that in its answer lies also the understanding of the pathogenesis of this disease. Several hypotheses have been made regarding the mechanism of the harmful effect of gluten in patients with nontropical sprue. They may be classified into two groups, those based on an antigenic role [3-51 and those supporting the possibility that gluten exerts a direct toxic effect in patients with this disease [&a]. Clinical observations and experimental studies attempting to elucidate the role of gluten in nontropical sprue have also given rise to hypotheses concerning the etiology of this condition. These hypotheses may also be classified into two groups, those based on allergic concepts, closely related to the concept of a possible antigenic role for gluten [3-51, and those based on the concept, favored by several groups of investigators [7,9-151, that the primary t We consider nontropical sprue to be the same entity as the celiac disease of children and synonymous with idiopathic steatorrhea, adult celiac disease, gluteninduced enteropathy and celiac sprue. The relationship, or lack of it, between tropical and nontropical sprue remains undetermined. defect in nontropical sprue is enzymatic and resides at the level of the intestinal mucosal cell. Recent observations on the presence of circulating antibodies to gluten or to its various fractions and to milk proteins in patients with nontropical sprue [5,76,77] have important theoretic implications and may have practical significance as well. Further study of these circulating antibodies is, therefore, warranted and particularly so since controversy has stemmed from the studies heretofore reported. The purpose of this study was to investigate the presence of circulating antibodies against gluten and milk fractions in patients with nontropical sprue, to correlate the presence or absence of these antibodies with the clinical status and previous treatment of the patients, and to evaluate the theoretic and practical implications of such findings.