A temperature-sensitive (ts) mutant of respiratory syncytial virus, which was unable to replicate at 37 C in vitro, was administered by the nasopharyngeal route to adults who had low levels of neutralizing antibody in their nasal secretions. The ts mutant appeared to be attenuated under these conditions as indicated by a decrease in infectivity and by the asymptomatic nature of the infections that occurred. The ts mutant was genetically stable in vivo, and there was no evidence of reversion to wild type after replication in the upper respiratory passages of the volunteers. Although the mutant appeared to be attenuated, it did induce a state of resistance to subsequent challenge with wild-type (virulent) virus. These encouraging results suggest that the ts mutant should be further evaluated as a candidate for a vaccine for prevention of serious respiratory syncytial viral disease in the lower respiratory tract of young infants.