The effect of several adamantane derivatives on the activity of virion-associated RNA-dependent RNA polymerase of fowl plague virus (FPV) and influenza B virus was studied in vitro. Some of the derivatives inhibited the activity of the polymerase by 60%. A correlation was established between the previously demonstrated capacity of these inhibitors to suppress orthomyxovirus reproduction in vivo and their ability to reduce the activity of virion-associated RNA-dependent RNA polymerase in vitro.