Certain genotypes of HPV have been recently implicated in the etiology of carcinoma of the uterine cervix. In order to determine whether HLA antigen-controlled immunoregulatory functions have a role in the pathogenesis of HPV infections, class I and II HLA antigen typing was carried out on a series of 96 randomly selected women who were part of a cohort of 530 women prospectively followed up for cervical HPV infections in our clinic since 1981. The frequency of the DQ3 antigen, which has previously been reported to be increased among cervical cancer patients, was decreased in our HPV patients compared with the control group of Finnish women, but it was slightly increased in HPV16-infected women (P = 0.0812). However, we were able to demonstrate that HLA-DR5 antigen is significantly increased (i) in patients with high grade cervical intraepithelial neoplasia (CIN) (P < 0.02), and (ii) in women harbouring the high risk HPV type 16 (P = 0.0003), thus confirming earlier reports of an association of this HLA antigen and cervical cancer. Such a close association between the high risk HPV type 16 with an HLA antigen might have important implications in the possible immunogenetic basis of the increased risk for squamous cell carcinoma of the uterine cervix.