This placebo-controlled, double-blind study was aimed to evaluate the clinical efficacy, safety and tolerability of human leukocyte interferon-alpha (2 x 10(6) IU/g) incorporated in a hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal warts in women. Preselected, subjects (n=60) who ranged between 18 and 50 years of age (mean 23.7), harbouring 275 vaginal warts (mean 4.6) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papillomavirus (HPV) infections were randomly divided into 2 parallel groups. A precoded tube (45 g), active or placebo, with disposable applicators and instructions was given to each patient for one week's usage. Patients were demonstrated how to inject 4 g of the trial medication deep into the vagina 2 times daily for 5 consecutive days per week. During the 4-week treatment period, patients were examined on a weekly basis. Cure was defined as absence of clinical signs of infection, as well as PCR and Southern blot hybridization confirmed negative HPV DNA on molecular assay. By the cessation of the therapy 41.7% patients and 44.4% intravaginal warts were cured. Code disclosure revealed that interferon-alpha (2 x 10(6) IU/g) in gel had cured 73.3% patients, and 79.3% intravaginal warts, while placebo healed 10% patients and 8.1% lesions (active gel versus placebo; P<0.0001). Fifty-one patients (85%) complained of no drug-related adverse reactions. Nine patients (15%) mostly in the interferon-alpha gel experienced non-objective, mild headache, tenderness, with transient increase in their body temperature (>38 degrees C). In conclusion, the findings showed that along with non-objective mild side effects, human leukocyte interferon-alpha (2 x 10(6) IU/g) in a hydrophilic gel is significantly more effective than placebo to cure intravaginal warts in women.