Recent studies have hypothesized that late-onset immune response may be mediated through Immunoglobulin G (IgG) and Immunoglobulin A (IgA) in common migraine. In the present study, measurements of serum concentrations IgD, IgA, IgE, IgM and IgG were obtained on samples of healthy controls and common migraineurs. No significant differences in concentration of any of the isotypes were found between groups. Correlational analysis between isotypes within groups demonstrated that whereas the relationships between IgD and IgG, IgD and IgA, and IgG and IgE were positive in the control group, the correlations between these variables in the migraineurs were negative (inverse). Moreover, the application of semi-partial correlational techniques to these relationships generated divergent models of regulatory process underlying isotype expression. In control subjects, IgD is involved in the expression of IgA and IgE, which are reciprocally related to each other and in turn affect the concentration of IgG. Common migraineurs were found to be characterized by a dysfunctional regulatory process as manifested in their pattern of isotype expression. IgD is involved in the independent expression of IgA, IgE or IgG, but IgA and IgE are not involved in the expression of IgG and there is no reciprocal relationship between IgA and IgE.