Purified carrier-free monoiodinated insulin (Ins*) alone or mixed with an excess of native insulin was injected into the vitelline vein of 17, 19 or 21 day-post coitum (d.p.c.) rat fetuses in utero. Several organs concentrated Ins* among which liver, kidneys, heart, jejuno-ileum and lungs. Their radioactivity was analyzed by gel chromatography and autohistoradiography. In the 3 age groups, the liver had the highest specific activity: binding was saturable, partly reversible, associated with the hepatocytes and to a lower extent with the liver hematopoietic cells. Liver maturation was essentially characterized by a progressively increasing rate of hormone internalization and degradation. In the lungs, high affinity and saturable binding was associated with the glycogen-laden cells of the bronchial tubes (pseudoglandular stage: 17 d.p.c. fetuses). Ins* binding was no longer observed in more mature surfactant synthetizing cells (canalicular, 19 d.p.c. and alveolar, 21 d.p.c. stages).In conclusion: 1. Insulin receptors ontogenesis occurs early in gestation. 2. During the last 5 days of intra-uterine life, cytodifferentiation differently affects insulin metabolism at the cellular level, inducing loss of insulin receptors (lungs) or maturation of post receptor steps (hepatocytes).