Ureaplasma species are the bacteria most frequently isolated from human amniotic fluid from asymptomatic pregnancies and placental infections. U. parvum serovars 3 and 6 are the most prevalent serovars isolated from men and women. We hypothesized that the effects of chronic ureaplasma infection of amniotic fluid on the fetus and chorioamnion are dependent on the serovar, the dose, and variation of the ureaplasma multiple banded antigen (MBA) and mba gene. We injected high or low dose U. parvum serovar 3, serovar 6 (or vehicle) intra-amniotically into pregnant ewes at 55 days of gestation (term = 150 days) and examined the chorioamnion, amniotic fluid, and fetal lung tissue of animals delivered by Cesarean section at 125 days of gestation. Variation of the multiple banded antigen/mba generated by serovar 3 and serovar 6 ureaplasmas in vivo were compared by PCR assay and western blot. Ureaplasma inoculums demonstrated only one (serovar 3) or two (serovar 6) MBA variants in vitro, but numerous antigenic variants were generated in vivo: serovar 6 passage 1 amniotic fluid cultures contained more MBA size variants than serovar 3 (P = 0.005); and ureaplasma titers were inversely related to the number of variants (P = 0.025). The severity of chorioamnionitis varied between animals. Low numbers of mba size variants (/=9 mba variants showed no/little inflammation. These differences in chorioamnion inflammation may explain why not all women with in utero Ureaplasma spp. experience adverse pregnancy outcomes.