[en] Cadmium caused a spike in cytoplasmic free [Ca⁺] ([Ca⁺]_i) similarly to bradykinin in cultured human skin fibroblasts. Cadmium increased [Ca²⁺]_i in the presence or absence of external Ca²⁺. After bradykinin produced a spike in [Ca²⁺]_i, the addition of cadmium had no effect on [Ca²⁺]_i indicating that cadmium and bradykinin release Ca²⁺ from the same intracellular pool. Cadmium triggered a concentration-dependent increase in ⁴⁵Ca²⁺ efflux. Half-maximal stimulation of efflux occurred at 0.1 μM cadmium. Certain other metals also stimulated ⁴⁵Ca²⁺ efflux. The potency order of the metals was Cd²⁺ > Co²⁺ > Ni²⁺ > Fe²⁺ > Mn²⁺. Zn²⁺ competitively inhibited Cd-evoked ⁴⁵Ca²⁺ efflux but had no effect on bradykinin-evoked efflux. Cadmium also decreased total cell Ca²⁺ by 50-60% within 2 min similarly to bradykinin. Decreasing external Na⁺ from 120 mM to 3 mM caused a spike in [Ca²⁺]_i, an 8-fold increase in ⁴⁵Ca²⁺ efflux, and rapidly decreased total cell Ca²⁺ by 40% similarly to cadmium and bradykinin. Decreasing external pH also increased [Ca²⁺]_i, stimulated ⁴⁵Ca²⁺ efflux, and decreased total cell Ca²⁺. The three unusual stimuli (cadmium, decreasing external Na⁺, and decreasing external pH) trigger rapid increases in [³H] inositol 1,4,5-trisphosphate (IP₃), which indicates that IP₃ is the intracellular messenger for release of stored Ca²⁺ by these three unusual stimuli. A single receptor appears to mediate the Ca²⁺ mobilizing response to all three stimuli