A comparison of identified sympathetic neurons in the isolated intact superior cervical ganglion (SCG) revealed that secretomotor, pilomotor and vasoconstrictor cells differ in their action potential mechanisms and in their postsynaptic ₂-adrenergic responses to 10 µM norepinephrine (NE). In normal saline, the half-width of the spike afterhyperpolarization (AHP) in secretomotor neurons (103.5 ± 6.2 ms) was double that recorded in vasoconstrictor neurons (47.7 ± 2.9 ms) and 1.5 times that in pilomotor neurons (71.4 ± 10.3 ms). Bath-applied NE reversibly inhibited the action potential repolarization shoulder, AHP amplitude and AHP duration in secretomotor and pilomotor neurons to a similar extent, but had no effect on vasoconstrictor neurons. The insensitivity of vasomotor neurons to NE was not an artifact produced by microelectrode recording because all three cell groups were similar in terms of resting potential and input resistance. Moreover, NE insensitivity was not a natural consequence of briefer AHP duration in vasoconstrictor cells. Adding 10 mM TEA⁺ caused marked accentuation of the shoulder and AHP duration in vasoconstrictor neurons and comparable changes in the other two cell types, but did not unmask any sign of NE sensitivity in the vasoconstrictors. However, the spike shoulder and AHP in vasoconstrictors were Cd²⁺-sensitive, blocked by -conotoxin, an N-type calcium channel antagonist, and inhibited by oxotremorine-M, a muscarinic receptor agonist. These data show that NE can differentially modulate functional subsets of mammalian sympathetic neurons and that NE insensitivity can serve as a practical experimental criterion for identification of vasomotor neurons in the isolated ganglion.