Human parainfluenza virus-type 1 (hPIV-1) is the most common cause of pediatric laryngotracheobronchitis (croup) and results in close to 30,000 US hospitalizations each year [Ped. Inf. Dis. J. 20 (2001) 646]. No effective vaccine is available. We examined murine PIV-1 (Sendai virus, SeV) as a live, xenotropic vaccine for the closely related human PIV-1 in a phase I, dose escalation study in healthy adults. Intranasal Sendai virus was uniformly well-tolerated and showed evidence of immunogenicity in three of nine vaccinees despite pre-existing, cross-reactive immunity presumably induced by previous exposure to human PIV-1. Results encourage future trials to evaluate the efficacy of Sendai virus in preventing human PIV-1 infection in infants and children.