Mechanisms of hemoglobin transition during bullfrog metamorphosis were investigated by labeling red blood cells from larvae (L-RBC) and from froglets (A-RBC) with a fluorescent dye, PKH26. The life span of the labeled L-RBC in systemic circulation was significantly shorter when they were injected into the animals at the metamorphic climax, compared to injection into pre- or postmetamorphic animals. The A-RBC had a long life span regardless of the metamorphic stage of the recipient animal. Therefore, L-RBC were selectively removed from the systemic circulation at the time of metamorphic climax. During climax, the labeled L-RBC were ingested by hepatic and splenic macrophages, indicating that macrophages are involved in the specific elimination of L-RBC.