The distribution of i.v. injected 125I-labeled epidermal growth factor (EGF) was examined in the rat. The uptake of radioactivity was examined for the following tissues: liver, kidney, skin, stomach, small intestine, colon, brain, submandibular gland, lung, spleen, and testis. 125I-EGF was cleared from the circulation within minutes. At 2.5 min after the injection only 7% of the label was left in the blood. Most of the label was found in the liver (52%), the kidneys (14%), the small intestine (11%) and the skin (7%). The other organs examined contained 1% or less of the radioactivity. The uptake of 125I-EGF per g tissue was markedly higher for the liver and kidneys than for the rest of the organs. By autoradiography 125I-EGF was found in the peripheral parts of the classical liver lobule, in the proximal tubules of the kidneys, in the surface epithelium of the stomach, and in the surface epithelium of the villi in the small intestine. In conclusion the present study showed that small doses of homologous EGF was cleared from the circulation of rats within minutes, mainly by the liver, the kidneys, and the small intestine.