To investigate the possible mechanisms by which interferon gamma (IFNgamma) affects pregnancy, the expression of class II major histocompatibility complex (MHC) antigens and cleavage of DNA that is a hallmark of apoptosis in the placenta were examined by molecular biochemical techniques, and progesterone levels were examined by radioimmunoassay. The semi-quantitative analysis with reverse transcription-polymerase chain reaction showed that the expression of MHC class II antigen in placenta increased when rabbits were treated with high doses of IFNgamma compared with the control. However, immunohistochemical study suggested that IFNgamma did not affect MHC class II expression in trophoblasts, but had a stimulatory effect on its expression in maternal decidua and placental lymphocytes. DNA fragmentation analysis and terminal deoxynucleotidyl mediated-deoxyuridine triphosphate nick end labeling (TUNEL) assay indicated that the cleavage of DNA was detected in the placenta in both normal and IFNgamma-treated pregnancy. Quantitative analysis of apoptotic cells revealed an increase in trophoblasts treated with IFNgamma compared to those in normal pregnancy. Moreover, progesterone, which plays an important role in pregnancy, was reduced significantly in rabbits treated with IFNgamma. The results suggested that IFNgamma exerted its deleterious effect on pregnancy by inducing apoptosis in trophoblasts and by reducing the production of progesterone.