Associations between the immune response and the severity of tick-borne infections are poorly understood. Objective. Assessment of the parameters of cytokines secretion, proliferative activity and cytogenetic instability in the mononuclear blood cell cultures of patients with tick-borne encephalitis febrile form and ixodid tick-borne borreliosis nonerythemal form at the onset of the disease. Patients and methods. We assessed 24 parameters in the phytohemagglutinin-stimulated mononuclear blood cell cultures from 25 patients with tick-borne encephalitis, 24 patients with ixodid tick-borne borreliosis, and from 14 healthy donors. Statistical analysis included the Mann–Whitney test, Pearson’s goodness-of-fit test, Spearman’s rank correlation, and ROC analysis. Results. The patients compared with the controls showed a suppression of the stimulated blast transformation, increases in the levels of the micronucleated T-lymphocytes and the secretion of not only pro-inflammatory cytokines – tumor necrosis factor (TNF)-α and interleukin (IL)-6, but IL-10 and IL-4 as well. Pyrexia levels were negatively correlated with the blast transformation and positively correlated with the micronucleated T-cells levels and pro-inflammatory cytokines secretion. The predictors for the diagnosis of tick-borne encephalitis compared with borreliosis were decreases in the blank and/or stimulated levels of blast transformation and the production of TNF-α, IL-6, interferon-γ as well as increases in the micronucleated T-cell levels and the secretion of IL-8 and IL-10. Conclusion. The results represent the features of the immune response reactions and its association with the severity of the clinical picture. Key words: blast transformation, ixodid tick-borne borreliosis, tick-borne encephalitis, micronucleus assay, mononuclear blood cells, phytohemagglutinin, cytokines