The mucosa that lines the upper respiratory and digestive pathways is protected by a secretory immune system which is under complex and only partly understood immunoregulatory control. B cells of relatively immature memory clones with a potential for J-chain expression, are initially stimulated in mucosa-associated lymphoid tissue (probably including the tonsils) and migrate thereafter through lymph and blood to glandular sites where they are subjected to terminal differentiation and become immunoglobulin (Ig)-producing immunocytes. Most locally produced Ig is normally dimeric IgA which is selectively transported through the serous type of glandular cells by means of an epithelial receptor protein called the secretory component (SC). IgM is also subjected to SC-mediated transport. In patients with selective IgA deficiency, secretory IgA is lacking, but may be satisfactorily replaced by protective secretory IgM. In other IgA-deficient patients, however, immunoregulatory compensation gives rise to a large number of IgD-producing cells in respiratory mucosa. IgD cannot act as a secretory antibody and these patients are prone to have recurrent infections. These observations show that there are large individual variations in the secretory immune system.