BACKGROUND Patients with common variable immunodeficiency often suffer from recurrent bacterial infections. Administration of immunoglobulins is a well-established treatment to reduce the frequency and severity of these infections. However, in patients with anti-IgA antibodies or side effects to previous immunoglobulin substitution therapy, administration of immunoglobulins may lead to anaphylactoid reactions. OBJECTIVE To describe the feasibility of immunoglobulin substitution therapy in patients with anti-IgA antibodies or side effects to previous immunoglobulins. METHODS A retrospective study was conducted in two university hospital outpatient clinics. Fourteen patients with common variable immunodeficiency were found to have circulating anti-IgA antibodies or have experienced severe reactions to previously administered blood products. RESULTS In eight out of 15 patients side effects to immunoglobulins and/or blood transfusions had occurred previously. In four patients these reactions were due to anti-IgA antibodies. No side effects were observed when human immunoglobulin 16% was given by subcutaneous infusion. In all patients with anti-IgA antibodies, as well as in those without, subcutaneous immunoglobulins were well tolerated. In some patients antibodies disappeared and therapy could be changed into intravenous immunoglobulin administration. CONCLUSIONS Patients with serious side effects to previous immunoglobulin therapy and/or blood transfusions can be safely treated with subcutaneous immunoglobulins and, if necessary, with intravenous immunoglobulins at a later point in time.