Publisher Summary This chapter discusses the autoimmunity in acquired dysgammaglobulinemia of chickens. The development of a line of chickens with inherited immunodeficiency has been recently reported. Examination of serum Ig levels from previous generations helped trace the defect to a single-line 3 male, an ancestor common to both line 140 and 142. This deficiency, analogous to human acquired agammaglobulinemia, is characterized by early normal Ig synthesis, followed by a late onset dysgammaglobulinemia. The expression of this abnormality is variable and may include generally elevated serum IgM and total absence or marked elevation of serum IgG. Selective backcrosses have shown that the dysgammaglobulinemia is highly heritable and is probably under the control of more than one gene. In an experiment described in the chapter, it was found that mating abnormal cocks with abnormal hens resulted in lower fertility than that of other mating combinations. A slight but not significant reduction in the hatchability was also noticed. Most significantly, there were a greater number of abnormal chicks produced when both parents were dysgammaglobulinemic.