This study addresses whether CD3-zeta suppression associated with cervical intraepithelial neoplasia (CIN) I, II, and III is mediated by a circulating factor and if this suppression is reversed following treatment. Serum was isolated from patients with CIN before and after curative therapy. Jurkat T cells were incubated with patient-derived sera for 4 days, and CD3-zeta expression was analyzed by western immunoblot. Sera from control female volunteers did not suppress CD3-zeta expression of Jurkat cells, while sera from women with CIN I, II, and III suppressed 58.9%, 75.3%, and 80.5%, respectively. Suppression observed in women with CIN I was significantly different from that observed with CIN II and III. Posttreatment zeta suppression was noted to be reversed in women with CIN II and III although the decreased suppression in CIN III patients was not statistically significant. Our study demonstrates that in vivo suppression of zeta chains in patients with CIN can be the result of a circulating factor. In vitro zeta expression increased in patients with CIN II and III after treatment, although the increase was only statistically significant in patients with CIN II.