Alkaline phosphatase isoenzymes in sera from patients with sickle cell anemia were separated by electrophoresis on starch gel. Physical and biochemical criteria identified bone alkaline phosphatase as the principal, although not necessarily the sole, enzyme fraction that increases during symptomatic sickle cell crises. Moreover, there appeared to be concordance between crisis severity, serum levels of alkaline phosphatase, and isoenzyme patterns; electrophoretic and biochemical abnormalities could be detected even when the patients were asymptomatic. The present data suggest that the serum alkaline phosphatase level may be an additional indicator of the degree, frequency, and persistence of tissue injuries that occur in sickle cell anemia.