This study investigated the differences in niacin skin flush responses between patients with schizophrenia, bipolar mania, and normal controls. We applied niacin patches of three concentrations (0.001 M, 0.01 M, and 0.1 M) to the skin of 61 patients with schizophrenia, 18 patients with bipolar mania, and 40 normal controls for 5 min. Flush responses were rated at 5, 10 and 15 min after application. Flush responses were significantly different among three groups at the concentrations of 0.1 M and 0.01 M at all of the three rating time points. The use of nicotine did not have significant influences on the flush responses. Absent response was significantly more prevalent in the schizophrenia group than in the other two groups, but was not significantly different between the bipolar and the control group. The greatest degree of differentiation in flush responses among groups occurred at the 0.01 M concentration, and the rating time point of 10 min with 49.2% of schizophrenic patients but only 7.5% of controls and 11.1% of bipolar patients not showing a flush response. The niacin skin test for schizophrenia had 49.2% sensitivity and 92.5% specificity compared with controls. This study found that absent response to niacin skin patch was specific to schizophrenia and independent of smoking status.