A rapid rate of clearance of circulating interferon has been observed in mice (Baron et al. 1966; Gresser et al. 1967; Subrahmanyan & Mims, 1966) and in rabbits (Ho & Postic, 1967) after a single injection of interferon. However, in a recent study (De Clercq, Nuwer & Merigan, 1970) the rate seemed to be slower after multiple intravenous injections of interferon. These observations are extended in this paper. Interferon was injected into the lateral tail vein of 2- to 4-week-old randomly bred Swiss-Webster albino mice. Animals were then bled at different times from the right retro-orbital plexus, and sera from two mice were pooled for each assay sample. Mouse interferon was produced in L-929 cells as described elsewhere (Hanna, Merigan & Jawetz, 1966) with the Cassell 73-t strain of Newcastle disease virus (NDV). After inactivation of residual NDV at pH 2 for 5 days, the tissue culture fluid was concentrated tenfold by pressure dialysis in a pressure cell (Amicon Corporation, Cambridge, Massachusetts) employing a UM-10 filter.