TASK-3 channels belong to the twin-pore-domain acid-sensitive K⁺ channel family and show close relationship with the TASK-1 and TASK-5 channels. It has been proposed that TASK-3 channels may have roles in the genesis and/or development of certain malignant tumours, although their exact roles are still not understood. In this study immunocytochemistry was performed to investigate the TASK-3 expression pattern of three melanoma cell lines maintained in tissue culture. The immortalised melanoma cell lines employed in the present study were obtained from either a primary melanoma tumour (WM35) or from its metastases (HT168 and M1) (for more details see Timar et al. 1999). The identity of the cells was demonstrated by using melanoma-specific markers (HMB45 and S100 protein). The validity of the present findings was confirmed by employing three different primary antibodies targeting different epitopes of the human TASK-3 channel and by applying preadsorption control experiments. All the findings described in this work were consistently reproducible with all three primary antibodies. All three melanoma cell lines demonstrated intense TASK-3-specific labelling, whose pattern and distribution showed time-dependent changes. The TASK-3 specific reaction was never confined to the surface membrane of the cells, but intense labelling could be demonstrated intracellularly as well. It was noted that the dividing, spherical cells exhibited an intense, homogenously distributed TASK-3-specific labelling in all three cell lines. The flat, multiprocessal cells, on the other hand, showed somewhat less powerful labelling, which mainly concentrated to the nuclear-perinuclear region of the cell as well as to the developing processes. Rather surprisingly, intense TASK-3-specific labelling could also be demonstrated within the nuclei of the melanoma cells in all three cell lines. The nuclear expression was the most prominent in the proliferating areas (in 10, low cell density visual fields the ratio of the TASK-3 positive nuclei was 99%; n = 280), whereas in the confluent regions only 14% of the nuclei showed TASK-3 positivity (n = 1,216). When the cell lines were exposed to an antimytotic agent (Mitomycin C) for 48 h, the proportion of the TASK-3-positive nuclei was markedly reduced, especially in the non-confluent areas. When 10-10 low density visual fields were compared, the proportion of the TASK-3 positive nuclei was 30 and 96% in the Mitomycin C-treated and control cultures, respectively. The effect of Ruthenium Red (RR) was also tested, as this substance is an inhibitor of the TASK-3 channels. Besides reducing the number of the surviving melanoma cells in a dose-dependent fashion, RR application induced prominent changes in the cell morphology: the proportion of the multipolar cells was reduced and 98% of the cells showed a distinct spherical appearance (100 mμM). Our results suggest that the inhibition of the cell-division affects the expression pattern of the TASK-3 channels, whereas interfering with the function of the TASK-3 channels may alter the cell development. These findings imply that there might be a connection between the TASK-3 channels and the cell-division.