We studied interferon (IFN) in the serum and CSF of 31 patients with multiple sclerosis. The sensitive IFN bioassay required only small volumes and detected IFN levels as low as 0.5 international units/ml (CSF) or 4 international units/ml (serum) of IFN. Two hundred twenty-eight paired CSF/serum samples were tested, and no IFN was found.