OBJECTIVE Our recent studies showed that lactoferrin seems to be down-regulated in endocervical adenocarcinomas. We extended those studies to examine the expression of transferrin (Tf) and its receptor (TfR) in endocervical carcinogenesis and any relationship to the expression of lactoferrin, steroid receptors and the proliferative index. METHODS A retrospective study was performed using sections prepared from paraffin-embedded, formalin-fixed surgical specimens of normal endocervix, endocervical adenocarcinoma and cervical adenocarcinoma in situ. Standard immunohistochemical techniques were used to localize Tf and its receptor in the normal and malignant endocervix. In situ detection of mRNA for Tf and the TfR was also performed. The relative intensity of the immunoreaction was estimated using digital computer image analysis. Statistical significance was tested by Student's t test. RESULTS No differences in the relative staining intensity for Tf and TfR proteins were noted between normal and neoplastic glands. However, quantitation revealed that a greater number of malignant glands stained positive for TfR than observed in the normal endocervix. Expression of Tf and TfR did not correlate with the expression of steroid receptors and lactoferrin or with the rate of proliferation. CONCLUSIONS We have demonstrated the expression of Tf and its receptor by both normal and malignant endocervical glands. The increased number of malignant endocervical glands expressing TfR may indicate a special requirement for Tf and the iron that it carries. Our data provide evidence for the existence of a Tf, TfR autocrine or paracrine circuit involved in the regulation of normal and abnormal endocervical physiology.