AIM To explore molecular biology developing mechanism of non-and-hyporesponder.METHODS Thirty children (3-7 years old) were selected whose anti-HBs titres were lower than 10min/mLand HBsAg, anti-HBc were negative. 843 children were defined as non-and-hyporesponders. Control groupswere 30 normal responders to HB vaccine. Experiment groups and control groups Peripheral venous bloodwas drawn in preservative-free heparin (25 U/mL), and unfractionated mononuclear cells were obtained byFicoll gradient centrifugation. Cell suspensions were routinely incubated in complete culture medium at 37℃for 1 h before cultured to eliminate cytophilic antibodies. Mononuclear cell concentration of cell suspensionsmust be geared to 1×105 cells/mL with complete culture medium, taking these cell suspensions (1 mL) intoflatbottom 24-well culture plates, then ConA 10 mg/L was added to wells and the plates were incubated at37C in a humidified atmosphere of 95% air and 5% CO2 for 48 h. This cell culture supernatants wereremoved to test tubes and level centrifugation (2000rpm) for 10 minutes, upper liquid was samples of IL-2 orIL-6. IL-2 or IL-6 activity was measured by CTLL-2 cells or 7TD1 cells toxin transfer test methods respectly.The results were expressed as stimulation index (SI) which represent the ratio of the mean counts per minute in quadruplicate well containing IL-2 (or IL-6) samples or IL-2 (or IL-6) standard solution to the meancounts per minute in quadruplicate wells containing cells and medium only.RRSULTS Interleukin-2 (IL-2) mean activity (74.5±64.1 U/mL) of the non-and-hyporesponders tohepatitis B vaccine in the 20 subjects was much less than that of the normal responder groups (298.0±101.1)to hepatitis B vaccine (t = 5.23, P<0.01); The correlation coefficient (r) between the anti-HBs levels andIL-2 activity in the 20 normal response to HB vaccine was 0.68 (r = 0.68, P<0.05). There was a positivecorrelation between the anti-HBs levels and IL-2 activity. Difference in interleukin-6 mean activity was noted in serum from subjects who responded to HB vaccinecompared with those who failed to respond. The responder groups (58.98±16.4) had a significantly higherIL-6 activity than the non-and-hyporesponder groups (30.10±12.4) (t =5.68, P<0.05). The correlationcoefficent of the IL-6 activity and titers of serum anti-HBs in the responder groups was 0.79 (P<0.05).CONCLUSION Some cytokines as IL-2 and IL-6 play an important role in the response to HB vaccine.