Exercise-associated hyponatremia (EAH) is a life-threatening electrolyte imbalance, biochemically defined by a blood sodium concentration ([Na+]) below 135 mmol/L. Because athletes die from brain swelling (encephalopathy) associated with severe EAH, most institutional review boards will not allow researchers to induce hyponatremia in laboratory settings. Accordingly, researchers must target athletes in field settings to investigate the risk factors, pathogenesis, and treatment of EAH. One-hundred-mile (161 km) mountain footraces, held in hot climates, provide the most favorable conditions for development of EAH. We thereby undertook an ambitious series of sodium balance studies during a 161-km ultramarathon to investigate the pathophysiology of EAH. In addition to testing runners pre- and post-race, we followed our runner participants—both on foot and in cars—through the Sierra Nevada mountains taking weights, drawing blood, and collecting food diaries, urine bags, and sweat patches. We also studied body composition and conducted a randomized controlled treatment trial at race finish. Daytime ambient temperatures were particularly hot (>40°C) on race day; thus, only 6 of 18 subjects completed the distance (one participant turned the wrong way after 90 miles [150 km] was disqualified from the race, but completed the study trial) within the 30-hr time limit. Thus, despite substantial subject attrition and data losses, research teams can still salvage novel findings when they embrace foresight, teamwork, and resilience during extreme circumstances.