The effects of extracellular Ca²⁺ ions on purinergic responses were examined in swine tracheal smooth muscle cells (TSMCs) in primary culture. ATP (1μM to 1mM) and α, β methylene adenosine 5'-triphosphate (α, β-Me ATP) (100μM and 1mM) concentration-dependently increased [Ca²⁺] in the presence and the absence of extracellular Ca²⁺ . Responses to ATP (10μM to 1mM) in the presence of extracellular Ca²⁺ were significantly larger than those in its absence (n=8), whereas those to α, β-Me ATP were not significantly different between the presence (n=7) and the absence (n=8) of extracellular Ca²⁺ . Responses to ATP (1mM) at extracellular Ca²⁺ concentration ([Ca²⁺] _o) of 10 and 5mM were significantly larger than that at extracellular EGTA concentration ([EGTA] _o) of 1mM (p<0.01, n=5), whereas the responses to α, β-Me ATP (1mM) at 10 and 5mM [Ca²⁺] _o were significantly smaller than that at [EGTA] _o of 1mM (p<0.05, n=5). Increasing [Ca²⁺] _o to 5mM after the application of either 1mM ATP (n=4) or 1mM α, β-Me ATP (n=4) in the absence of extracellular Ca²⁺ (1mM [EGTA] _o) further increased [Ca²⁺] _i, though the increases in [Ca²⁺] _i, by agonists in 1mM [EGTA] _o had been already maximal. Incubating cells for 300s in 5mM [Ca²⁺] _o before the application of ATP (1mM) significantly increased the response to the drug than that obtained by incubating cells for 6sec in 5mM [Ca²⁺] _o before the drug application (p<0.01, n=4). However, α, β-Me ATP (1mM) induced similar responses by incubating cells for 30 or 300s in 5mM [Ca²⁺] _o to that by incubating them for 6s. These results suggest that the effect of α, β-Me ATP in swine TSMCs in primary culture is mainly through Ca²⁺ release and that its effect on Ca²⁺ entry is smaller than other nucleotides.