Objective. Evaluation of adaptive physiological responses to passive hyperthermia (PН) procedures, including serum concentrations of irisin, brain neurotrophic factor (BDNF), cortisol and insulin-like growth factor (IGF1) in healthy young people before and after a two-week course of PH procedures. Methods. 15 young men completed a 2-week course of 10 PH procedures: 40 minutes in a capsule of infrared heating of the body, at 65–80oC (the head is outside of the capsule). Heart rate, blood pressure, SpO2, temperature and body weight were recorded before and after PH procedures. The level of hormones in the blood serum was evaluated in the dynamics of the first and tenth sessions. It was then compared with data obtained during placebo procedures performed with the same frequency and duration 3 weeks before the course of PH. Results. During all PH procedures, the values of systolic blood pressure and SpO2 decreased, heart rate and body temperature increased by an average of 2.0-3.2˚C. Values of the physiological stress index was in the range of 4-6 units. Small increase in cortisol level was observed only after the 1st procedure. These facts indicate moderate thermal stress in PH. Increase in sweat loss during the course was the sign of thermal adaptation. After the first and 10th PH procedures, there was an increase of irisin concentrations (by 16% and 18.8%, respectively) and BDNF (by 8.2% and 7%). Moreover, after the 10th PH, a direct relationship between the dynamics of these myokines: rΔIrisin-ΔBDNF=0.52 (p=0.04) was registered. No changes were observed after placebo procedures. Conclusion. PH procedures during the two-week course caused the development of moderate heat stress. Adaptive shifts developed in response to this stress. The concentrations of irisin and BDNF increased in the dynamics of the first and final procedures. It is assumed that irisin and BDNF are participants in positive cross – effects of adaptation to PH. The results obtained are important for the development of adaptive medicine technologies.