Envelope glycoproteins of human parainfluenza virus type 3 (PIV-3) were selectively solubilized with n-octyl β-D-glucopyranoside and reconstituted into lipid vesicles by dialysis of the detergent. The efficacy of the glycoprotein preparation as a subunit vaccine when administered to hamsters intranasally or subcutaneously was compared. Animals receiving four intranasal immunizations with 5 µg of the glycoprotein preparation were completely resistant to challenge infection. Only partial protection, however, was observed in animals immunized subcutaneously with the same dose of antigen. The local glycoprotein-specific IgA response was significantly higher in intranasally immunized animals and was implicated in resistance to challenge infection. © 1988 by The University of Chicago.