Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects in healthy rats and humans as well as patients with dysfunction of neuroendocrine-immune complex, encephalopatia and chronic pyelonephritis. The purpose of this study is clarification of the role of neuro-endocrine factors in their immunotropic activity in patients with chronic pyelonephritis. Materials and Methods. The object of observation were 17 men (aged 24-70 years) with chronic pyelonephritis in remission. The plasma levels and urinary excretion of nitrogenous metabolites as well as parameters of immunity and its neuro-endocrine regulation twice (on admission and after balneotherapy at the Truskavets’ Spa) was performed. Results. Judging by the multiple correlation coefficient, uricosuria exhibits maximal neuro-endocrine activity (R=0,780), followed by bilirubinemia (R=0,742), creatinineuria (R=0,692), uricemia (R=0,636), creatinineemia (R=0,632), urea excretion (R=0,536), instead urea plasma correlate with neuro-endocrine parameters insignificantly (R=0,360). Nitrogenous metabolites together determine the state of neuro-endocrine regulation by 94,2%, which, in turn, determine the state of immunity by 99,9%. Conclusion. Nitrogenous metabolites carry out immunomodulation in different ways: directly through aryl hydrocarbon (bilirubin), toll-like and adenosine (uric acid) receptors of immunocytes; through modulation of the activity of neurons of the autonomous nervous system and endocrinocytes with subsequent neuro-endocrine immunomodulation; and also, apparently, due to an off-receptor effect on neurons, endocrinocytes and immunocytes (urea and creatinine).