Problem: To assess the modulation of T-cell CD3-zeta chain expression by a factor in the sera of women, prior to egg retrieval and 14 days after an in vitro fertilization (IVF) and to delineate the mechanism, of this modulation. Method of study: In this prospective study, blood samples were obtained from 17 patients during an IVF cycle, prior to human chorionic gonadotropin (hCG), and 14 days after embryo return. Serum was incubated with cultured T-lymphocytes (Jurkat cells) for 96 hr and expression of CD3-zeta chain was evaluated. Results: Eight patients had a positive serum hCG titer 14 days after retrieval, while nine patients had a negative hCG titer. Serum from pregnant patients significantly suppressed CD3-zeta chain expression as compared with their sample prior to retrieval (85.6+/-6.2%), while subjects not becoming pregnant failed to suppress zeta expression (99.1+/-0.9%. P<0.0001). Conclusion: A factor capable of suppressing TcR/CD3-zeta expression can be detected in the sera of pregnant women 14 days after embryo retrieval. Loss of zeta chain was associated with the induction of apoptosis.