The objective: To develop an effective programme of combination immunotherapy for treatment of immunocompromised girls suffering from chronic nonspecific vulvovaginitis (CNVV), taking into account specified impairments of the functioning of the immune system and interferon (IFN) system. Patients and methods: We observed 25 girls aged 3 to 4 years, suffering from recurrent CNVV in the exacerbation period. The control group consisted of 12 conditionally healthy girls of the same age. Immunophenotyping of T and B lymphocytes, natural killer cells (NKC) was employed to assess the immune system (IS). The phagocytic and microbicidal function of neutrophil granulocytes (NG) was examined with detection of the number of actively phagocytic NG (%PhAN, PhC, PhI), assessment of digestive activity (%D, DI). NADPH oxidase activity of NG was determined by parameters of spontaneous and stimulated NBT tests (St. aureus), taking into account % of formazan-positive NG (%FPC), average cytochemical index (ACI), by the %FPCst/%FPCsp ratio mobilisation coefficient (MC) was calculated. Using methods of enzyme-linked immunosorbent assay, the levels of serum immunoglobulins (IgA, IgM, IgG, IgE) and interferons (IFN-α, -γ) were tested. Results: In immunocompromised girls suffering from CNVV, deficiency of cytotoxic T lymphocytes, NKC, serum IFN-α, IFN-γ, IgA, IgM, IgG and defects of NG phagocytic activity were found. Taking into account the diagnosed disorders a 10-week programme of combination immunotherapy of girls was developed with the use of local and systemic therapy with recombinant human interferon α2b in combination with antioxidants (viferon) and glucosaminyl muramyl dipeptide (licopid). Analysis of the clinical effectiveness after 1-year follow-up showed that after the administered combination immunotherapy the incidence of CNVV exacerbations was reduced by 3.4 times from 6.2 to 1.8 times per year (p < 0.05) and the duration of exacerbations decreased from 12-14 days to 7-8 days. The clinical picture of CNVV exacerbations developing after a complex of therapeutic measures was characterised by smoother symptoms. Also, the incidence of ARVI decreased from 14.8 to 5.2 episodes per year, p < 0.05, and their duration was reduced from 10-14 days and more to 5 days. Positive clinical effects of combination immunotherapy were accompanied by a positive dynamics of changes in the immune system: normalisation of a previously low lymphocyte count with the cytotoxic function (CD3+CD8+; CD3-CD16+CD56+), recovery of the absolute values of CD3-CD19+ and against this background the level of serum IgA, IgG, previously decreased by 2 times, recovery of actively phagocytic NG (%PhAN); NG engulfing capacity (PhC and PhI). Conclusion: The developed programme of combination immunotherapy with inclusion of viferon and licopid permitted to obtain a positive clinico-immunological and protective effect (catamnestic follow-up for 1 year) in immunocompromised girls with recurrent CHVV and recurrent respiratory tract infections. © 2018 Dynasty Publishing House. All rights reserved.