Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved. Altered expression of the ets family transcription factors erg and ets-2 was found associated with the development of cervical carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell line, CX16-2, which has HPV integrated at a translocation breakpoint t(19;21) involving 21q22.2-22.3, where these genes have been mapped. Six of 10 cervical carcinoma cell lines overexpressed ets-2 RNA suggesting an association of overexpression with cervical cell neoplasia. A clonally related pair of cervical carcinoma cell lines, C-4I and C-4II, showed differential expression of erg and ets-2. C-4I overexpressed ets-2 RNA compared to normal cervical cells and C-4II. C-4II expressed a 5.3 kb erg transcript not seen in C-4I, ectocervical cells or other cervical carcinoma cell lines examined. Pulsed field gel electrophoresis was used to analyse changes in DNA fragments related to structural changes and to construct a physical map encompassing erg and ets-2. Alterations in erg and ets-2 RNA expression in each of three different cell lines examined were associated with translocations. Association between altered expression of erg and ets-2 and altered regional structural suggests that these genes are important targets in cervical carcinogenesis.