The metastatic ability of prostate cancer cells involves differential expression of ionic mechanisms. In the present study, using electrophysiological recordings and intracellular Ca 2+ measurements, we investigated Ca 2+ related signalling in two rat prostate cancer (MAT-LyLu and AT-2) cell lines of markedly different metastatic potential. Whole-cell voltage clamp experiments indicated the absence of an inward current carried through voltage-dependent Ca 2+ channels in either cell line. A Ca 2+ -dependent component was also absent in the voltage-activated outward K + currents. Indo-1 microfluorimetry confirmed these results and also revealed marked differences in the resting level of intracellular Ca 2+ and the ability of the two cell lines to regulate intracellular Ca 2+ . The weakly metastatic AT-2 cells displayed a significantly higher resting intracellular Ca 2+ than the related but strongly metastatic MAT-LyLu cell line. Increasing extracellular K + decreased intracellular Ca 2+ in the AT-2 but had no effect on intracellular Ca 2+ levels in the MAT-LyLu cells. Furthermore, increasing extracellular Ca 2+ increased intracellular Ca 2+ in AT-2 but, again, had no effect on MAT-LyLu cells. These results suggested the presence of a tonic, voltage-independent Ca 2+ permeation mechanism operating specifically in the AT-2 cells. The influx of Ca 2+ into the AT-2 cells was suppressed by both CdCl 2 (100–300μM) and SKF-96365 (10–30μM). It is concluded that the strongly metastatic MAT-LyLu cell line lacks a voltage-independent basal Ca 2+ influx mechanism that is present in the weakly metastatic AT-2 cells.