The calcium influx plays a key role in processes of activation, proliferation and cytokine synthesis in human T lymphocytes. Although the calcium currents in blood cells are well studied, the molecular identity of ionic channels involved in such an important process as T-cell activation and normal/pathological cell proliferation remains elusive. Several members of transient receptor potential (TRP) channel family were shown to play a role in changes of [Ca2+]in in blood cells, however the properties and expression profiles of these channels in human lymphocytes are not yet fully determined. In our previous study, using RT-PCR and Western blot analyses we have shown the expression of TRPV6 (transient receptor potential vanilloid type 6) channels in Jurkat T- cells and in normal human blood lymphocytes (HBLs), isolated from the peripheral blood of healthy volunteers. Moreover, it was found that the levels of mRNA and protein expression of TRPV6 were significantly higher in malignant T-cells than in quiescent HBLs. In this study we performed electrophysiological and immunofluorescent experiments to reinforce our hypothesis that TRPV6 channels could be involved in human blood lymphocytes proliferation. We used outside-out patch-clamp recordings to search for TRPV6 channels in quiescent lymphocytes, phytohemagglutinin (PHA)-treated (48h) lymphocytes and Jurkat cells. TRPV6 single channels recording was assessed in divalent free solution at negative membrane potential (-70 mV), and the channels activity was reduced in presence of nonselective inhibitor of TRPV6 channels, Ruthenium Red (IC50=10µM). Overall, single TRPV6 channel activity was obtained in 77% (17 out of 22) of outside-out patches in Jurkat cells; in 83% (5 out of 6) of outside-out patches in PHA-treated HBLs; and in 40% (2 out of 5) of outside-out patches in quiescent HBLs. Next, immunofluorescence method was employed to examine the TRPV6 channel density and subcellular distribution in these cells. Immunofluorescence signal was detected on the plasma membrane of T- cells and HBLs and the intensity of the signal was substantially higher in Jurkat and PHA-treated HBLs than in quiescent HBLs. Thus, both electrophysiological and immunofluorescence data showed that TRPV6 channel activity and TRPV6 channel density are significantly higher in transformed lymphocytes (Jurkat) compared to quiescent lymphocytes. Moreover number of TRPV6 channels increases after activation of HBLs to proliferation. In whole, present findings suggest a potential role of TRPV6 in normal and/or pathological proliferation of human blood lymphocytes. We hope that in the future, TRPV6 can be considered as a potential molecular marker for early diagnosis of T-cells malignancy.