The distribution of histamine and histidine decarboxylase activity in epidermis and upper dermis, mid dermis and lower dermis in human allergic contact dermatitis was studied by direct microchemical analysis of individual serial microtome sections with histological correlations. The occurrence of preformed histamine and of histidine decarboxylase activity were established for 5 patients with allergic contact dermatitis and the results compared with those obtained in 6 control subjects. The concentration of preformed histamine was significantly increased throughout all of the histologic regions of the dermatitic skin. The 48-hour old inflammatory reaction, invoked by patch testing in patients with allergic contact dermatitis, produced a significant increase in histidine decarboxylase activity in the upper layers of the skin, but had no effect in the lower dermis.