Clinical study was conducted on 77 adult patients with hypersensitivity to honey bee venom (HBV) to determine clinical characteristics and pathogenesis of hypersensitivity to HBV as well as the effect of specific immunotherapy(ITS) with HBV on several clinical and immunological parameters. The patients studied (43 women and 34 men of age ranging between 18-61 years with a mean age at 30 years) were divided into two groups: Group 1-44 patients with a history of anaphylactic shock following honey bee sting, who received specific immunotherapy with HBV. Group 2-33 patients hypersensitive to HBV(9 people reacted with severe anaphylactic systemic reaction, while others had skin reactions) who were not treated by ITS method. In all patients skin tests with HBV allergen were conducted before and at various stages of immunotherapy. Specific IgE (I1), s-IgG4 (I1), total IgE, IgG, IgA, IgM, C3c, C4 were estimated in sera samples obtained at the beginning, during the course and at the end of ITS. Dynamics of changes of these parameters were studied during a 3-year period of ITS. The challenge tests were conducted at the end of the treatment. 86.9% of treated patients reacted with IgE-mediated reactions. They showed elevated levels of s-IgE before immunotherapy, and significant decrease in s-IgE and increase in s-IgG4 titers after ITS. 10.4% of patients showed clinical symptoms of anaphylaxis, but non-IgE mediated. IgE titer in these patients was < or = 0.2 IU/ml and has not significantly changed during immunotherapy. s-IgG, levels were in these patients below 2 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)