MG-63 cells, a line derived from an osteosarcoma, produced high yields of interferon after superinduction with polyinosinic acid·polycytidylic acid, cycloheximide, and actinomycin D. Advantages of MG-63 cells over diploid fibroblasts as a substrate are: no requirement for aging between confluency and induction, no requirement for priming, and 3.7-fold higher yields per square centimeter of culture surface. Physicochemically and biologically, MG-63 cell interferon resembles fibroblast rather than leukocyte interferon.