The isotypes of IgG, IgG1, IgG2, IgG3, and IgG4 were determined in immunoglobulin preparations and the effect on serum levels of treated patients. Serum IgG subclass deficiencies were recorded in different patient groups: (1) IgG2-IgG4 deficiency was associated with IgA deficiency. (2) IgG2-IgG4 deficiency was found in patients with ataxia telangiectasia. (3) Low IgG2 levels were recorded in patients with SLE; one of these patients with recurrent pericarditis was treated with immunoglobulin with good results. (4) Low IgG2 and/or low IgG3 levels were found in patients with juvenile diabetes mellitus. (5) Mothers giving birth to severely group B streptococci infected infants showed low levels of IgG subclasses indicating that the newborns were IgG subclass deficient at birth. (6) In a prospective study of children with recurrent otitis media aged 12 and 32 months the IgG2 levels were significantly reduced in the group with considerably high otitis proneness. In patients with IgG2-IgG4 deficiency, absence of antibodies to polysaccharide antigen teichoic acid and the protein antigen alpha-toxin of staphylococci was demonstrated. Imbalanced IgG subclass pattern with increased IgG4 was recorded in patients with different diseases such as atopic diseases and also in combination with increased IgE, Henoch-Schönlein vasculitis, idiopathic pulmonary hemosiderosis, chronic mucocutaneous candidiasis, and in patients with Trichuris trichiura infection.