SUMMARYWe have examined the effect of five local anaesthetics (dibucaine, tetracaine, cocaine, lignocaine and procaine) and five phenothiazine tranquillizers (trifluoperazine, fluphenazine, promethazine, chlorpromazine and diphenhydramine) on cell fusion induced by viruses. When used at physiologically relevant concentrations, all drugs significantly inhibited cell fusion without impairing virus replication. It is suggested that these drugs inhibit cell fusion by occupying sites within the plasma membrane which must be vacant in order for membrane fusion to occur. Inhibition of cell fusion by these drugs provides experimental support for the suggestions put forward elsewbere that events in membrane fusion and membrane depolarization are similar.