The use of laser Doppler flowmetry (LDF) in determining changes in cutaneous blood flow following intradermal injection of histamine has been investigated in this double-blind study. In eight subjects blood flow (LDF) and weal-and-flare area (planimetry) were measured at regular intervals for 1 hr following 50-μl injections of different concentrations of histamine (6.5 ± 10−5 -6.5 ± 10−3 M) and saline. The mean maximum increase in LDF values over the flare was at least nine-fold greater than the baseline values for all three concentrations of histamine injected. When the LDF values observed at different sites were integrated to obtain the ‘LDF response’ it was possible to demonstrate concentration-related increases in blood flow and to differentiate clearly between the different concentrations of histamine and saline for up to 30 min after injection. During this period, the repeatability and the time course of the LDF response was comparable with that of the flare area. These studies suggest that the non-invasive technique of LDF is a sensitive and reproducible method for quantifying the changes in cutaneous blood flow that occurs for the first 30 min after intradermal injection of histamine.