It is widely believed that erythrocyte sedimentation rate (ESR) determinations are of little value in sickle cell disease since the rate is comparatively slow. Using the Westergren method, uncorrected, we performed ESR's in 44 children with sickle cell disease during painful crises, periods of infection and during intercrisis visits when they were otherwise well. Comparison of these three groups revealed that in 19 children with sickle cell disease the average ESR was 7.9 mm (range 3-21 mm) during inter-crisis periods. In 10 of 12 children with proven infection, the ESR was above 20 mm (average 38.3 mm), while among 13 children with painful crises the ESR was above 20 mm in only 5 (average 21 mm). The average values in patients with painful crisis or with infection were significantly higher than those in the inter-crisis periods. In general, the ESR's were higher in children with infection than in those experiencing painful crises. There was no relationship between the ESR in these patients and the degree of anemia. The findings suggest that an elevated ESR (above 20 mm) is a useful diagnostic parameter suggesting infection in patients with sickle cell disease.