Human parvovirus B19 can cause congenital infection with variable morbidity and mortality in the fetus and neonate. Although much information exists on the B19-specific antibody response in pregnant women, little information is available describing the cell-mediated immune (CMI) response at the maternal-fetal interface. The focus of this study was to characterize the CMI response within placentas from women who seroconverted to B19 during their pregnancies and compare it to controls. Immunohistochemical techniques were used to identify the various immune cells and the inflammatory cytokine present within placental tissue sections. Group 1 consisted of placentas from 25 women whose pregnancies were complicated by B19 infection; 6 women with good outcome (near-term or term delivery), and 19 with poor outcome (spontaneous abortion, nonimmune hydrops fetalis, or fetal death). Group 2 consisted of placentas from 20 women whose pregnancies were complicated with nonimmune hydrops fetalis of known, noninfectious etiology. Group 3 consisted of placentas from eight women whose pregnancies ended in either term delivery or elective abortion. The results of the study revealed a statistically significant increase in the number of CD3-positive T cells present within placentas from group 1 compared to group 2 or 3 (13.3 versus 2 and 1, respectively) (P < 0.001). In addition, the inflammatory cytokine interleukin 2 was detected in every placenta within group 1 but was absent from all placentas evaluated from groups 2 and 3. Together, these findings demonstrate evidence for an inflammation-mediated cellular immune response within placentas from women whose pregnancies are complicated with B19 infection.