The role of cytokines in protecting against human papillomavirus (HPV) and HPV-associated disease is not fully understood. We compared the frequency of the interleukin (IL)-10 polymorphism (G allele) at position --1082 and the distribution of GG/GA/AA genotypes among 116 HPV-positive women, grouped according to their cervical cytological profiles, with 119 HPV-negative controls with normal smears. No difference was observed in genotype frequency between the groups. Among women in the HPV-positive, smear-normal group, who were re-tested for HPV after 12 months, there was a significant inverse association between presence of at least one variant G allele (high activity) and HPV persistence (OR per G allele = 0.082 [95% CI 0.009-0.73], P= 0.001; after controlling for ethnicity). This association remained significant after controlling for age, smoking and hormonal contraception (OR = 0.028 [95% CI 0.001-0.66], P= 0.001). This preliminary study suggests that higher levels of IL-10 may prevent cervical neoplasia through their role in eliminating HPV.