The in vivo fate of radiolabeled recombinant human leukocyte A interferon (125I-rIFNαA) and intramolecular hybrid A/D (125I-rIFN-αA/D Bgl) were studied, following iv injection into CD, mice. Trichloroacetic acid (TCA) precipitatile radioactivity, as well as antiviral activity, were measured in sera and several organ extracts. The results obtained by bioassay were very similar to those obtained by measuring the TCA precipitable radioactivity. The kidney and liver showed preferential uptake of these 125I-IFNs. These studies indicate the feasibility of using radioiodinated IFNs in tissue distribution and pharmacokinetic evaluations.