Women carrying serological HLA-DQ3 specificity have previously been found to have an increased risk of developing squamous cell carcinoma of the cervix. Here we report the distribution of DQA1 and DQB1 genes in 158 Norwegian patients with squamous cell carcinoma of the cervix and in 186 ethnically matched controls. The DQA1 typing revealed an increase of the DQA1*030X allele among the patients compared to the controls [odds ratio (OR) = 1.77] and a decreased frequency of DQA1*0201 among the patients (OR = 0.57). DQB1*0301 was increased (OR = 1.81) and DQB1*0201 was decreased (OR = 0.64) among the patients compared to the controls. Among the patients, 67% carried genes encoding DQ3 (DQB1*0301, DQB1*0302, or DQB1*0303) compared to 51% of the controls, which gives an odds ratio of 2.0, significant both in corrected and uncorrected statistical analysis. The haplotype DQA1*0201-DQB1*0201 was decreased among the patients compared to the controls (OR = 0.38). Human papillomavirus (HPV) has been demonstrated to be a contributing factor in the development of this carcinoma. Primary tumors (fresh frozen) from 65 of the patients were analyzed for the presence of HPV 16 and HPV 18 by polymerase chain reaction. The DQA1-DQB1 haplotypes were distributed randomly among the patients with HPV 16 or HPV 18 present in their tumors so no association was found. Neither was there any difference between DQ3-positive and DQ3-negative patients in the frequency of HPV 16- or HPV 18-positive tumors. DQB1*03 showed no independent significant association with relapse-free survival.(ABSTRACT TRUNCATED AT 250 WORDS)