Study objectives: To determine if and to what extent the total iron-binding capacity (TIBC) would increase following an iron overload, and to identify specific iron-binding proteins that might be responsible for the increased TIBC. Design: A prospective laboratory investigation. Setting: A certified regional poison control center. Participants: Six healthy adult male volunteers. Measurements and main results: All volunteers ingested 20 mg/kg of elemental iron. Blood samples were drawn at hourly intervals for eight hours and analyzed for serum iron, TIBC, transferrin, ferritin, lactoferrin, glucose, bicarbonate, and WBC. Within two hours of ingestion, subjects developed symptoms of toxicity, including nausea, lightheadedness, vomiting, severe crampy abdominal pain, and voluminous diarrhea. The TIBC was statistically significantly increased at all points measured from one to six hours. Despite rising above 300-mu-g/dL in five of six subjects, the serum iron never exceeded the TIBC in any subject. Transferrin and ferritin did not increase to account for the increased TIBC. The lactoferrin levels did increase, but they did not correlate with significant increases in the TIBC. Conclusions: Twenty mg/kg of elemental iron caused clinical toxicity in this study, and after iron overload the colorimetric TIBC increased by unknown mechanisms.