Different reactivities of small blood vessels to the histamine released by exogenous and endogenous substances may play a role in the regional variations of the elicited cutaneous response. To study the regional dependence of cutaneous blood flow in response to histamine, the compound was administered intradermally (prick introduction), thereby bypassing the spatially dependent penetration process. The induced response was quantified with cutaneous blood flow measurements utilizing laser Doppler flowmetry. Extent of response and time parameters were compared. Three anatomical sites, the back, volar side of the forearm, and ankle, were studied on 20 volunteers (10 men and 10 women, age 24-34). For comparison, topical administration was also performed. Significant differences in the measured responses at the three sites were observed: the increase of the cutaneous blood flow on the back was greater than the forearm (p < 0.01 prick test, p < 0.05 topical application), and that of both sites was greater than the ankle (p < 0.01 prick test, p < 0.05 topical application). There were no significant differences among the different sites in time parameters and no gender variations. As expected, the time required to reach maximum response was shorter for the intradermal method as compared to the topical application on the back (p < 0.001) and forearm (p < 0.05). On the other hand, the time required to decrease to 50% of maximum response was not different for the intradermal and topical methods of histamine application. These blood vessel response observations may provide initial insight into inherent functional differences influencing cutaneous manifestations of endogenous and exogenous diseases.