The magnitude of the response to interferons and the requirement for individual elements in the promoter of the H-2Dd gene were shown to be cell-specific and dependent on the type of interferon used. Three DNA sequences in the promoter were found to bind murine nuclear factors. Two of these sequences are in functionally defined enhancer regions and also bind to the transcription factor AP-1. The third sequence is part of the region involved in interferon regulation and is homologous to the enhancer element of the interferon beta gene. A model for interferon regulation of H-2 promoters is discussed.