Acute chest syndrome (ACS) is an important cause of mortality and morbidity in children with sickle cell disease (SCD). An association between asthma and ACS has been reported. Our aims were to determine whether asthma was more common in SCD children than controls and the relationship of the timing of the SCD children's first ACS episode to a diagnosis of asthma. One hundred and sixty-five SCD children median age 8.2 (range 0.3-17.3) years and 151 similar ethnic origin and aged controls were prospectively recruited into the study and a detailed history was taken from all of the children to determine if they were taking anti-asthma medication. The medical records of the SCD children were examined to assess whether they had an ACS episode, the age this episode occurred and when any diagnosis of asthma had been made. A similar proportion of the SCD children and controls were taking anti-asthma medication (7% and 9%). Thirty-three SCD children had at least one ACS episode. More of the children who had an ACS compared to those who had not were taking anti-asthma medication (P=0.02). The ACS children had been diagnosed as asthmatic at a median of 3.5 (range 0.5-7) years prior to their first ACS episode. In conclusion, these results suggest asthma exacerbations may predispose to ACS episodes.