Mast cells are involved in the physiological immune response as well as in inflammatory processes. Ca signals were analyzed after 4-5 weeks of IL-3-dependent differentiation, when >97 % of cultured cells expressed both FcåRI and c-Kit as analyzed by FACS. In non-stimulated cells, voltage ramps from -100 to +100 mV did not elicit any consistent currents, indicating that there is no dominant ion channel activity under resting conditions. Store-depletion by InsP3 consistently activated CRAC channels with a mean current amplitude of -1 pA/pF. CRAC channels were inhibited by 80% through 100 nM BTP2, a selective CRAC channel blocker. However, Ca signals following store depletion were not blocked to the same extend. We postulated that other ion channels besides CRAC channels must contribute to Ca signals in mast cells. We could not detect any other store-operated ion channels instead but found three Ca-activated conductances: a Ca-activated K+ channel and two Ca-activated non-selective ion channels. The Ca-activated K+ channel can hyperpolarize the membrane potential, thereby increasing Ca signals. One of the Ca-activated cation channels is not permeable to Ca, whereas the other one can probably conduct Ca. We conclude that in contrast to T-lymphocytes, in which CRAC channels are the dominant Ca influx source, several Ca/cation channels contribute to Ca influx in bone-marrow derived mast cells.