The role of histamine in regulating excitability of sympathetic preganglionic neurons (SPN) and the expression of histamine receptor mRNA in SPN was investigated using whole-cell patch clamp electrophysiological recording techniques combined with single-cell RT-PCR in transverse neonatal rat spinal cord slices. Bath application of histamine (100µM) or the H₁ receptor agonist histamine trifluoromethyl toluidide dimaleate (HTMT; 10µM) induced membrane depolarization associated with a decrease in membrane conductance in the majority (70%) of SPN tested, via activation of postsynaptic H₁ receptors negatively coupled to one or more unidentified K⁺ conductances. Histamine and HTMT application also induced or increased the amplitude and/or frequency of membrane potential oscillations in electrotonically coupled SPN. The H₂ receptor agonist, dimaprit (10µM) or the H₃ receptor agonist, imetit (100nM) were without significant effect on the membrane properties of SPN. Histamine responses were sensitive to the H₁ receptor antagonist triprolidine (10µM) and the non-selective potassium channel blocker barium (1mM) but were unaffected by the H₂ receptor antagonist tiotidine (10µM) and the H₃ receptor antagonist, clobenpropit (5µM). Single cell RT-PCR revealed mRNA expression for H₁ receptors in 75% of SPN tested, with no expression of mRNA for H₂, H₃ or H₄ receptors. These data represent the first demonstration of H₁ receptor expression in SPN, and suggest histamine acts to regulate excitability of these neurons via a direct postsynaptic effect on H₁ receptors.