The effect of external gamma-irradiation on 59Fe release from alveolar macrophages (AMs) that had ingested 59Fe-iron hydroxide colloid was determined in C3H mice and Wistar rats with an in vitro assay system. The release of 59Fe from AM was increased by irradiation in mice but not in rats. A significant increase in 59Fe release was seen in mouse AM cultured for 72 hrs after irradiation at a dose of more than 25 Gy; but, graded doses of gamma-irradiation up to 100 Gy had no effect on 59Fe release from rat AMs. This difference between mice and rats may be attributable to the magnitude of death of or damage to AM because the survival of AMs assessed by vital staining with crystal violet decreased much more in mice than in rats.