Elevated vasodilatory response (blushing) to social situations is characteristic of social phobia (SP). A relatively unexplored basis for this phenomenon is alteration in underlying vasodilatory mechanisms. To investigate this possibility, we evaluated the vasodilatory response induced by methyl nicotinate (niacin ester derivative) in 31 generalized SP patients and 41 matched healthy volunteers (HV). A patch impregnated with 0, 0.1, 0.5, 1, and 10 mM methyl nicotinate was applied to the forearm or face of subjects for 1 min, followed by 20-min laser Doppler spectroscopy blood flow monitoring. Blood flow stimulation with 1 and 10 mM methyl nicotinate was significantly reduced in SP patients by 35 and 17%, respectively. Induced blood flow was negatively correlated with patients' Leibowitz Social Phobia Scale (LSAS) at 1 and 10 mM doses. Furthermore, the maximal rate of change of vasodilatory reaction was correlated with symptom scores at 1 and 10 mM doses. Induced increases in the arm and face blood flow measurements correlated, supporting the external validity of the former location. Generalized SP patients vasodilate less to topical methyl nicotinate challenges, with effect amplification in severely ill patients. Although the mechanism for this is unclear, we propose desensitization of the prostaglandin-mediated vasodilating system as an explanation. Neuropsychopharmacology (2003) 28, 1846-1851, advance online publication, 23 July 2003; doi:10.1038/sj.npp.1300227