We surveyed historical and laboratory data for 127 IgA-deficient patients (ages 2-67), referred to an immunology clinic; the commonest medical history was recurrent respiratory infections (50%), followed by autoimmunity (28%) asthma and allergy (13%). Fifty-two subjects have been given a pneumococcal vaccination; vaccine responses to 12 serotypes were significantly related to serum IgG2 levels (P = 0.004). Six immunized IgA/IgG2-deficient subjects produced insignificant amounts of antibodies to these pneumococcal serotypes; 10 others with normal IgG2 levels also had subnormal vaccine responses. IgA-deficient patients who had at least one B8 allele (n = 19) had a significantly greater response to this vaccine than the HLA-B8-negative subjects (n = 24) (P = 0.024). There was no relationship between a history of recurring infections and pneumococcal vaccine responses; HLA status was not related to a history of autoimmunity.