Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), cell division was retarded, whereas only minimal toxic cellular effects were observed. The appearance of progeny virus from the cell cultures exposed to these anesthetics was decreased in a dose-related manner. Incorporation of [(3)H]uridine into measles virus nucleocapsids also decreased progressively with increasing anesthetic concentrations. In comparing the inhibition of measles virus replication in the presence of halothane (2-bromo-2-chloro,1,1,1-trifluoroethane), enflurane, or isoflurane, it was found that both inhibition of the appearance of infectious virus at 48 h postinfection and incorporation of [(3)H]uridine into measles virus nucleocapsids were proportional to the anesthetic concentrations. An equivalent degree of effect was produced by anesthetically equivalent concentrations of the three anesthetics (minimal alveolar concentration) but not by absolute concentrations. In addition, recovery of infectious virus synthesis from the inhibition encountered during exposure of infected BSC cells to halothane or isoflurane was also investigated. In cultures exposed to halothane or enflurane, recovery of infectious virus synthesis was rapid and complete. Recovery of virus synthesis was slower after isoflurane removal and did not reach the peak control titers of infected cultures not exposed to the anesthetic. Treatment with halothane resulted in the formation of a preponderance of slowly sedimenting virus nucleocapsid particles which contained less than full-length ribonucleic acids after anesthetic removal. Neither enflurane nor isoflurane treatment of BSC cultures resulted in the formation of significant levels of these slowly sedimenting particles with short genomes after anesthetic removal.