Studies of ontogenesis contribute to better understanding of regulatory events underlying the striking heterogeneity in B-cell differentiation pathways employed in the human mucosal immune system. This disparity is probably explained by exogenous environmental factors, although regional differences probably also exist in accessory cells and cytokines involved in local immune responses. IgA deficiency signifies a heterogeneous syndrome but is basically a manifestation of a defect in B-cell differentiation. The immaturity of the IgA system revealed in this disorder bears a striking resemblance to that seen in newborn infants. It may therefore be worthwhile to consider IgA deficiency in relation to the ontogeny of mucosal immunity.