Anesthetized rats were treated with saline, antiinsulin receptor serum, or antiinsulin serum, and the biodistribution of high pressure liquid chromatography-purified '23I-Tyr A14-insulin was studied by scintillation scanning. Time activity curves over organs of interest were calibrated by sacrificing the rats at the end of the experiment and directly determining the radioactivity in the blood, liver, and kidneys. Saline-treated rats exhibited normal insulin biodistribution. The highest concentration of "HI-insulin was found in the liver, and reached 30% of total injected dose between 3 and 5 min after injection. After this peak, activity rapidly decreased with a t1/2 of 6 min. Activity of "23I-insulin in kidney showed a more gradual rise and fall and was -15% of injected dose at its maximum.In rats treated with antiinsulin antiserum, insulin biodistribution was markedly altered. Peak