In briefAlthough sickle cell trait is generally benign and consistent with peak athleticism, it poses a small risk of gross hematuria and splenic infarction at altitude. More alarming is the growing evidence that, in some people with sickle cell trait, maximal exercise—especially in hot weather or when new at altitude—can evoke a life-threatening syndrome of sickling, fulminant rhabdomyolysis, lactic acidosis, collapse, acute renal failure, and hyperkalemia. More than 30 such cases are described, along with practical tips for recognition and prevention.