Association between non-European variants of human papillomavirus (HPV) type 16 (HPV-16) and HPV-18 and cervical lesions has been suggested. To compare the P105 promoter activity among 6 HPV-18 variants, their complete long control regions (LCRs), as well as that of HeLa cells, were cloned upstream of the luciferase gene and transiently transfected in C33 cells. Whereas the B18-2 European variant showed the lowest promoter activity, the Asian-Amerindian variant, B18-3, had the highest activity. All variants tested were more active than the P97 HPV-16 prototype promoter. Differences in the LCR that impact P105 promoter activity could be responsible for the observed variability in oncogenic potential.