It is important to measure the rate of haemolysis in patients with sickle cell disease (SCD) to identify aplastic crises and indirectly assess the rate of vaso-occlusion and sequestration. The aim of this study was to assess whether end-tidal carbon monoxide (ETCOc) levels in children with sickle cell disease (SCD) could be measured reproducibly, reflected haemolysis and whether they were elevated compared to those of similarly aged, ethnic matched children without SCD (controls). ETCOc levels were measured non-invasively in 87 SCD children (age range 2.3-17.6 years) and 26 age and ethnic origin matched healthy controls using an electro-chemical sensor. The within- and between- occasion reproducibilities were assessed in ten and 15 SCD children respectively. ETCOc levels of 15 SCD children undergoing regular transfusions were related to carboxyhaemoglobin, haemoglobin and bilirubin levels. The within and between occasions' mean intrasubject coefficients of reproducibility were 5% and 18% respectively. Positive correlations were found between the ETCOc and carboxyhaemoglobin ( P =0.007) and bilirubin ( P =0.02) levels, and a significant negative correlation between the ETCOc and haemoglobin ( P =0.0002) levels. The mean and SD ETCOc levels of the SCD children (4.9 ppm; SD 1.7 ppm) were significantly higher than that of the controls (mean 1.3 ppm; SD 0.4 ppm) (difference between means 3.60; 95% C.I. 2.93-4.28; P <0.0001). CONCLUSIONS These results suggest that measurement of end-tidal carbon monoxide levels is a reliable and useful method to monitor haemolysis in children with sickle cell disease.