Hemoglobin distribution width (HDW) is a measurement of the heterogeneity of the red cell hemoglobin concentration as determined by the Technicon H1 automatic counter. The utility of this measurement for patients with sickle cell disease was assessed in 275 samples from 61 patients. We found that patients with sickle cell disease in steady state had an elevated HDW (3.89 +/- 0.82 gm/dl) compared with the normal range of 2.2 to 3.2 gm/dl, and that this value correlated strongly with the number of dense red cells (r = 0.72, p less than 1 x 10(-10]. When HDW was determined daily for patients with SS in painful crisis, the decline in dense cells observed during this event was paralleled by a decrease in HDW. The percent of dense cells fell from steady state levels of 10.0% +/- 9.5% to 5.7% +/- 4.9% at the beginning (days 1 through 3) to 3.1% +/- 2.0% at the end of painful crisis (days 6 through 9). HDW decreased from the steady state value of 3.89 +/- 0.82 gm/dl to 3.44 +/- 0.73 gm/dl at the beginning of crisis and fell further to 3.14 +/- 0.40 gm/dl at the end. We conclude that HDW is a rapid and reliable assessment of the percent of dense cells in sickle cell disease and is a useful objective parameter to follow in sickle cell crisis.