Histamine-induced cutaneous wheal responses were measured in 24 healthy subjects. The effect of the potent H₁ blocker, hydroxyzine HCI, the H₂ blocker, cimetidine, and the two drugs in combination was determined. The H₁ blocker alone produced a mean wheal suppression of 77%(p<0.005). The H₂ blocker alone produced a mean wheal suppression of 35%(p<0.01). The H₁ plus H₂ blocker produced 79% suppression. But the augmented suppression of H₁ plus H₂ blocker vs H₁ blocker was not statistically significant (p>0.05). The result provide evidence that H₂ receptors are present in the human cutaneous blood vessel, but additional studies must be performed to determine the significance of combined H₁ and H₂ blockade over H₁ blocker alone in suppression of histamine-induced wheal formation.