Chlamydia trachomatis infections can occur early in life and may result in long-term sequelae. To assess the feasibility of implementing a vaccine in newborns, groups of 2-day-old BALB/c mice were immunized intranasally (i.n.) with 1x10(4) inclusion forming units (IFU) of C. trachomatis mouse pneumonitis (MoPn). As a control, newborn mice were sham-immunized i.n. with minimal essential medium. In the vaccinated animals, strong Chlamydia-specific humoral and cell-mediated immune responses were observed. Six weeks after immunization, mice were challenged with MoPn i.n. or intravaginally (i.vag.). For the i.n. challenge, mice were inoculated with 10(4) or 10(5)IFU of MoPn per mouse, and in the case of the i.vag. challenge, each animal received 10(6)IFU. By day 10 post-infection (p.i.), the vaccinated mice challenged i.n. with 10(4)IFU, had gained an average of 6.7+/-1% of their body weight. In contrast, the sham-immunized mice had lost 14.9+/-1% of their weight (P<0.05). The mean number of IFU/lungs in the vaccinated animals was 800+/-300, while for the sham-immunized mice was 211+/-49x10(6) (P<0.05). Significant differences between the Chlamydia-vaccinated and the sham-immunized mice were also found in the groups challenged with 10(5)IFU. In the mice challenged i.vag., a significant decrease in the number of mice with positive cultures, and the intensity and duration of vaginal shedding was noted in the vaccinated mice compared to the sham-immunized mice (P<0.05). In conclusion, these results indicate that vaccination of neonatal mice can result in a protective response against a subsequent pulmonary or genital challenge with Chlamydia.