BACKGROUND Colour differences in photographs can be enhanced using a digital image-processing technique called LYYN. OBJECTIVE To investigate colour changes in the histamine wheal after skin prick tests (SPTs). METHODS Histamine SPTs were performed on the forearm of six medical students, and the reactions of the skin were photographed every 2min for 30min. Colour differences in the photographs were then enhanced using the LYYN technique. These images were processed using ImageJ to yield numerical values. RESULTS In the LYYN-processed images, there was a rapid colour change in the histamine wheals between the 18th and the 20th minute (P<0.01). Histamine perfusion in isolated rabbit ears indicated vasodilatation in post-capillary vessels and desensitized histamine 1 (H1) receptors after a mean of 17min. It is possible that a similar desensitization takes place in the human histamine wheal, and a study of two histamine SPTs 90 min apart at the same site supports this hypothesis. CONCLUSION The LYYN technique was sensitive enough to discover a rapid colour change in the histamine wheal, a change that has not been described before.