The prescribing information for nitrofurantoin states that patients with glucose-6-phosphate dehydrogenase deficiency may experience hemolysis following administration of the drug. Although there is no doubt that this statement is qualitatively correct, the degree of risk in the general population of patients has not been previously quantified. This study was designed to estimate the degree of risk of a clinically important hemolytic reaction to nitrofurantoin by means of a retrospective analysis of the Norwich Eaton adverse reaction database. Since 1953, approximately 130 million courses of nitrofurantoin therapy have been distributed in the U.S. alone. The database contained 127 reports of hemolytic reactions; a "worst-case" estimate of the incidence rate was 1 in 100,000 courses of therapy. Considering the extensive usage of nitrofurantoin, clinically important hemolytic reactions appeared to be very rare. For the cases in which outcome was recorded, complete recovery occurred in 87 percent of patients. Although nitrofurantoin is contraindicated after the onset of labor and in infants less than one month old, no well-documented cases of hemolytic reactions in neonates were identified.