AbstractEffective treatment is not currently available for suppressing the recurrences of genital herpes simplex virus (HSV) infections. Since intravenous immunoglobulins (IVIG) proved useful against HSV in experimental models, we treated patients with very high frequency of HSV genital recurrences (more than 15 episodes per year) with IVIG (400 mg/Kg every fourth week). The control group was treated with intermittent oral acyclovir (800 mg twice a day for one week every month). Both groups were treated for six months and, then, patients were followed-up to further six months.Both IVIG and acyclovir were effective in reducing the frequency of HSV genital recurrences as compared to base-line. However, patients treated with IVIG had a more striking reduction in the frequency of recurrences as well as both a shorter mean duration and a minor severity of the lesions as compared to acyclovir-treated patients. Furthermore, we found a trend indicating IVIG as more effective in reducing the viral load. Since in IVIG-recipients we found a strong increase of peripheral blood lymphocytes with natural killer (NK) surface phenotype, we suggest that the clinical effectiveness of IVIG treatment is probably mediated via the expansion of NK cell populations.Our study indicates that the treatment with IVIG is an effective and safe tool for suppressing the recurrences of genital HSV infections.