Respiratory syncytial virus (RSV) is a leading cause of respiratory disease among infants, the elderly and immunocompromised adults. In this study, we assessed the effects of [alpha]-galactosylceramide, a known immunoregulatory lipid, on liposomal RSV vaccine-induced responses in BALB/c mice subsequently challenged with RSV. Liposomes containing a recombinant fragment of the RSV G protein were prepared with and without [alpha]-galactosylceramide and used to immunize mice by the intranasal route. The inclusion of [alpha]-galactosylceramide in the liposomal formulation caused a dramatic reduction in bronchoalveolar lavage neutrophils, but also an increase in eosinophils, following subsequent RSV challenge. The reduction in neutrophils was specific to mice receiving [alpha]-galactosylceramide-containing liposomes and was not reproduced in mice administered liposomes containing another [alpha]-galactosyl lipid, [alpha]-galactosylphosphatidylglyceroylalkylamine. Lung IL-13 mRNA levels were particularly elevated in mice administered [alpha]-galactosylceramide-containing liposomes followed by RSV challenge. This study demonstrates a striking ability of [alpha]-galactosylceramide to modulate the cellular airway infiltrate in mice immunized with liposomal RSV vaccine followed by RSV challenge.