Pulmonary function tests in adults with sickle cell disease have shown a restrictive pattern that has been attributed to the sequelae of acute chest syndrome (ACS). We compared pulmonary function test results in 37 children with sickle cell anemia (20 with SS hemoglobin (HbSS), 14 with SC hemoglobin, and 3 with S beta hemoglobin) with those in 22 control subjects matched for sex, race, and height and compared pulmonary function in patients with and without a history of ACS. Of the 10 patients with a history of ACS, all but one had HbSS. Pulmonary function tests measured forced vital capacity (FVC), the diffusion capacity of carbon monoxide, and the plethysmographic determination of lung volumes. The FVC and forced expiratory volume in 1 second (FEV1), expressed as the percentage of the predicted value, were significantly less for those with HbSS with or without a history of ACS than for control subjects (p < 0.05), but the FEV1/FVC ratio, an index of airway obstruction, was normal in all groups. Total lung capacity was also significantly lower in patients with HbSS with or without a history of ACS than in control subjects (p < 0.05), but the ratio of residual volume to total lung capacity, another index of airway obstruction, was normal. We conclude that children with sickle cell disease, particularly those with HbSS, may have abnormally small lungs that function normally relative to their size; clustering of ACS episodes is not specifically associated with the observed abnormality.