We identified antibody deficiencies in 9 of 13 infection-prone children with Wolf-Hirschhorn syndrome (4p-monosomy). Eight of the immunodeficient children were identified by a questionnaire sent to 190 families with an affected child. Two of the children had common variable immunodeficiency, one had IgA and IgG2 subclass deficiency, three had IgA deficiency, and three had impaired polysaccharide responsiveness. T-cell immunity was normal. The association of antibody defects with Wolf-Hirschhorn syndrome suggests a regulatory gene within the deleted chromosome region that affects the B cell system.