The research objective was to study interrelation of maintenance of α-defensins 1—3 and a hypoxia-inducible factor 1-alpha (HIF-1α) in gingival liquid of patients with caries. Materials and methods. 75 patients with the diagnosis dentine caries were enrolled in the study and divided into two groups: in group 1 (n=30) caries was diagnosed in earlier untreated tooth, the 2nd group (n=45) included patients with the recurrence of carious process (in earlier treated tooth). Controls involved 25 caries-free individuals. The level of α-defensins 1—3 was studied in gingival fluid by ELISA method. Results. The level of α-defensins 1—3 and antimicrobic peptide in gingival liquid in group 2 was 28 and 36% higher than in the 1st group, correspondingly (p<0.001). Concentration of HIF-1α in gingival liquid in the 2nd group was almost twice higher (p<0.001) than in group 1 and 82% higher than in controls (p<0.001), while in group 1 it decreased by 11% when compared to controls (p<0.001). All controls showed a close correlation between the level of α-defensins 1—3 and HIF-1α in gingival fluid (R=0.78, p<0.001), not observed in group 1 (R=0.32, p>0.05) but statistically significant in group 2 (R=0.78, p<0.001). Thus, the recurrence of carious process in caries-associated tooth is associated with the hypoxia-dependent activation of a congenital antimicrobial immunity by means of accumulation of HIF-1α and pronounced increase of α-defensins 1—3 in gingival fluid.