We studied the dependence of climatotherapy effectiveness in patients with chronic heart failure (functional classes 0-II) on Ca²⁺-ATPase, phospholamban, β₁-adrenoceptor, and insulin-like growth factor 1 gene polymorphisms and possible interaction of these genes during the realization of the effect of climatotherapy. The effectiveness of climatotherapy depended on polymorphism of the studied genes; the maximum effect was attained in patients with the GG polymorphism of the Ca²⁺-ATPase gene, GT polymorphism of the phospholamban gene, ArgGly polymorphism of the β₁-adrenoceptor gene, and 19/19 polymorphism of the insulin-like growth factor 1 gene. We demonstrated additive interaction of Ca²⁺-ATPase and β₁-adrenoceptor genes during the realization of the cardiotonic effect of climatotherapy.