Is sickle cell trait (SCT) a risk factor for heat stroke and splenic infarction? Yes. Is SCT a risk factor for stroke? Evidently not. While the absence of evidence is not evidence of absence, there is, in short, no compelling evidence that SCT is a risk factor for stroke. Many articles and reviews of the risks of carrier status estimate that SCT affects 2.5 million African Americans, but SCT may have actually affected only a handful of individuals, such as those who have appeared in mostly isolated case reports. Most of the 2.5 million people who carry the sickle hemoglobin mutation remain unaffected. In the past several decades, SCT has been described in conjunction with common conditions such as migraine1 and depression2 as well as with unusual or even sensational situations (eg, SCT in a white Jewish family presenting as splenic infarction at high altitude3). However, the mutation is so prevalent (as it is in an estimated 8% of the African American population and 0.08% of the non–African American population)4 that a chance association with all diseases is certain.