Priapism, although uncommon in the general population, is one of the many serious complications associated with sickle cell disease (SCD). Few studies have described the clinical and hematologic characteristics of individuals with priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease, we assembled 273 case subjects with priapism and 979 control subjects. Case subjects, compared with control subjects, had significantly lower levels of hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate aminotransferase; and higher reticulocyte, white blood cell, and platelet counts. These findings suggest an association of priapism with increased hemolysis. Hemolysis decreases the availability of circulating nitric oxide, which plays an important role in erectile function.