Somatodendritic release of dopamine (DA) in midbrain represents a novel form of intercellular signaling that inherently differs from classic axon-terminal release. Here we report marked differences in the Ca(2+) dependence and time course of stimulated increases in extracellular DA concentration ([DA](o)) between the substantia nigra pars compacta (SNc) and striatum. Evoked [DA](o) was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry in brain slices. In striatum, pulse-train stimulation (10 Hz, 30 pulses) failed to evoke detectable [DA](o) in 0 or 0.5 mm Ca(2+) but elicited robust release in 1.5 mm Ca(2+). Release increased progressively in 2.0 and 2.4 mm Ca(2+). In sharp contrast, evoked [DA](o) in SNc was nearly half-maximal in 0 mm Ca(2+) and increased significantly in 0.5 mm Ca(2+). Surprisingly, somatodendritic release was maximal in 1.5 mm Ca(2+), with no change in 2.0 or 2.4 mm Ca(2+). Additionally, after single-pulse stimulation, evoked [DA](o) in striatum reached a maximum (t(max)) in <200 msec, whereas in SNc, [DA](o) continued to rise for 2-3 sec. Similarly, the time for [DA](o) to decay to 50% of maximum (t(50)) was 12-fold longer in SNc than striatum. A delayed t(max) in SNc compared with striatum persisted when DA uptake was inhibited by GBR-12909 and D(2) autoreceptors were blocked by sulpiride, although these agents eliminated the difference in t(50). Together, these data implicate different release mechanisms in striatum and SNc, with minimal Ca(2+) required to trigger prolonged DA release in SNc. Coupled with limited uptake, prolonged somatodendritic release would facilitate DA-mediated volume transmission in midbrain.