Intranasal inoculation of 12 young adult mice (strain TO) with Mycoplasma pulmonis protected all of them against vaginal colonization when they were challenged intravaginally 60 days later with the same mycoplasmal strain. In contrast, all 15 mice without a respiratory infection became colonized vaginally (geometric mean titre [GMT] 4·6 × 106 colour-changing units [c.c.u.]) when challenged in the same way. The GMT of serum antibody, measured by a micro-immunofluorescence technique, prior to challenge was 200 and 8 for the oropharyngeally infected and unexposed mice, respectively. The GMT of antibody in vaginal washings from the two groups was 6 and 3, respectively. All four nude BALB/c mice were susceptible to vaginal colonization (GMT 5·6 × 106 c.c.u.) after oropharyngeal infection (GMT 5·1 × 104 c.c.u.) resulting from intranasal inoculation, as were all six nude mice (vaginal GMT 1·4 × 107 c.c.u.) that had not been inoculated intranasally. In contrast, all ten of their immunocompetent counterparts were resistant to vaginal colonization after oropharyngeal infection (GMT 1·3 × 103 c.c.u.), whereas all nine such mice that had not been infected oropharyngeally were susceptible to vaginal colonization (GMT 7·6 × 106 c.c.u.). These results show the important role that a respiratory infection has in protecting the vagina against colonization and that protection is dependent on a functioning T-lymphocyte system.