This study estimated the number and cost of hospitalizations associated with sickle cell disease in the U.S..|To estimate the number of hospitalizations per year in the U.S. of people with sickle cell disease, the authors used data for the years 1989 through 1993 from national hospital discharge surveys conducted by the National Center for Health Statistics. The authors derived cost estimates using data from a 1992 national hospital discharge survey conducted by the Agency for Health Care Policy and Research and a 1992 survey of physicians conducted by the American Medical Association. During the years 1989 through 1993, there were on average an estimated 75,000 hospitalizations per year of children and adults with sickle cell disease. The average direct cost per hospitalization (in 1996 dollars) was estimated at $6300, for a total direct cost of $475 million per year. In 66% of hospital discharge records, government programs were listed as the expected principal source of payment. The cost of hospitalizations associated with sickle cell disease is substantial. Because government programs pay most of this cost, further government-funded research to develop interventions that prevent complications of the disease has great potential for cost savings as well as for reducing the suffering of those afflicted with this painful genetic disorder. These national cost estimates contribute to an understanding of the impact of sickle cell disease and should be useful in establishing research priorities.