Histamine is implicated in urinary bladder dysfunction as an inflammatory mediator driving sensory nerve hypersensitivity. However, histamine's direct influence on smooth muscle has not been thoroughly investigated. We hypothesized that histamine directly contracts urinary bladder smooth muscle (UBSM) independent of effects on nerves. Single cell qRT-PCR determined that only histamine H1 and H2 receptors were expressed on UBSM cells. In isolated tissue bath experiments, histamine (200 µM) caused a highly variable and rapidly desensitizing contraction that was completely abolished by the H1 receptor antagonist fexofenadine (5 µM) and the Gq/11 inhibitor YM254890 (1 µM). Neither the muscarinic receptor antagonist atropine (1 µM), the Na+ channel blocker tetrodotoxin (1 µM), nor the TRPV1 antagonist capsazepine (10 µM) altered responses to histamine, suggesting nerve activation was not involved. UBSM desensitization to histamine was not due to receptor internalization, as neither the cholesterol depleting agent methyl-b-cyclodextrin (10 mM), the dynamin mediated endocytosis inhibitor dynasore (100 µM), nor the clathrin mediated endocytosis inhibitor pitstop2 (15 µM) augmented or prolonged histamine contractions. Buffer from desensitized tissues still contracted histamine-naïve tissues, revealing that histamine was not metabolized. Prolonged exposure to histamine also had no effect on contractions due to electrical field stimulation, suggesting both efferent nerve and UBSM excitability were unchanged. Together, these data suggest that histamine, while able to transiently contract UBSM, does not have a lasting effect on UBSM excitability or responses to efferent nerve input. Thus, any acute effects of histamine directly on UBSM contractility are unlikely to alter urinary bladder function.