The increased incidence of lymphoma in celiac sprue (CS) is well documented, and the risk of developing this malignancy is 40-100-fold greater than in the general population. The author believes that gluten may also be at the root of lymphomas in asymptomatic and latent celiac sprue, as well. Among the 20-30% of the population which has the HLA factors most common in celiac, increased intestinal permeability leads to absorption of macromolecular peptides with opioid activity, which derive from pepsin digests of wheat. The presence, in the bloodstream, of these peptides may increase the risk of lymphomas for the entire hereditary group, which includes CS. Several processes contribute to the effect that is herein hypothesized, including opioid attachment at the hypothalamic-pituitary-adrenal axis (HPA), and subsequent downregulation of production of natural killer cells. This may offer an explanation for our longstanding awareness that there is an 'impaired lymphocyte reactivity against tumor cells in patients with coeliac disease' which may also apply to first-degree relatives with the same HLA markers.