Human papillomavirus (HPV) proteins E6 & E7 are considered to be the constitutively expressed neoantigens in a vast majority of cervical squamous intraepithelial lesions and cancers. Data available from in-vitro, animal, and small clinical trials suggest that the immunological properties of interferon gamma might enhance early viral protein presentation, thus stimulating a cytotoxic response. In order to study this effect in vivo we undertook a trial in which 20 women with a definite diagnosis of cervical intraepithelial neoplasia (CIN) grade I or II with coexistent high-risk HPV infection (detected by the Hybrid Capture System) underwent four months observation followed by intracervical administration of INFgamma in cases without spontaneous regression (17 cases). Human recombinant interferon gamma 1-b (Imukin) was administered intracervically four times in equal doses in two-day intervals to a total dose of 6,000,000 IU. The results of therapy were verified by punch biopsy evaluation and HPV-DNA testing two months after completion, and revealed a complete response in nine women (complete regression of CIN and remission of HPV infection in 53% of treated cases) and partial response in four cases (lower grade of CIN or/and remission of HPV infection--23.5%). The differences between spontaneous (before treatment) and treatment-related regressions were significant at p < 0.05. We conclude that in selected cases (mainly young women who have not completed their procreation and are compliant with the therapy) a conservative approach to CIN management with intracervical IFNgamma injections seems to be a valuable method.