Pulmonary involvement has been documented in thalassemia major (TM). We studied 12 patients with TM before and 24 hr after transfusion to evaluate the effect of transfusion on baseline lung function. Personal and family histories of respiratory illnesses were obtained by a questionnaire. Spirometry and carbon monoxide diffusion capacity (KCO) measurements were made. Blood gases (PO2 and SO2) were determined on arterialized samples. Baseline expiratory volumes and flows were within normal range in all patients. Transfusion resulted in a significant reduction of forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25 and 75% vital capacity (FEF25-75%). In two subgroups of patients identified by the questionnaire, those with no history of airway disease had normal baseline flows and no posttransfusion changes; those with history of airway obstruction had lower pretransfusion flows and significantly decreased posttransfusion FEV1 and FEF25-75%. The mean pretransfusion KCO value of 80% predicted for the whole group, significantly increased after transfusion (P < 0.05). Blood gases also significantly increased after transfusion (P < 0.05). When tested for the spirometric response to albuterol, patients with a history of asthma had a slightly greater increase in FEV1 and FEF25-75% than those who had never had asthma. We conclude that in our small study group, transfusion resulted in improved gas exchange and lung perfusion. The effect on flow limitation evident in some patients could, in part, be related to a preexisting bronchial hyperreactivity. Accurate evaluation of pulmonary function and of bronchial reactivity is advisable for patients with TM.