OBJECTIVE We investigated in a pregnant rabbit model the effects of intravaginal inoculation of type la group B streptococci and antibiotic intervention. METHODS We inoculated 10(4) to 10(6) cfu of type la group B streptococci into the upper vagina hysteroscopically at day 21 to 27 of a 31-day gestation. Initially we studied the natural history in 23 animals and then allocated the next 31 animals to receive either no therapy or ampicillin-sulbactam intramuscularly beginning immediately after inoculation. Outcomes were delivery, fever, positive cultures for group B streptococci, any live fetuses, and maternal death. RESULTS Without antibiotic treatment upper vaginal inoculation led to frequent complications, namely, fever in 44% (15/34), delivery in 41% (14/34), positive endometrial cultures in 47% (15/32), and positive blood cultures in 26% (7/27). Live fetuses were present in only 53% (18/34). Animals treated with antibiotics were significantly less likely to have fever (p < 0.01), positive endometrial cultures (p < 0.01), or positive blood cultures (p = 0.03) and were more likely to have a live fetus (p = 0.04) than untreated animals were. CONCLUSIONS Upper vaginal inoculation with type la group B streptococci in the rabbit led to an ascending infection of the upper genital tract, causing serious adverse outcomes in 40% with bacteremia in 26%. Early antibiotic intervention significantly improved outcomes. The susceptibility of the rabbit to ascending perinatal group B streptococci infection makes it an appealing model for further work pertinent to human disease.