Hydrochloric acid catalyzes the formation of fluorophores in the histochemical condensation reaction between gaseous formaldehyde and certain phenylethylamines and indolylethylamines. Thus, when the formaldehyde reaction is carried out in the presence of minute amounts of HCl gas, 3-methoxy-4-hydroxyphenylethylamine, 3,4-dimethoxyphenylalanine and tryptamine displayed a fluorescence yield approximately 20-200 times higher than that obtained after standard formaldehyde treatment in normal air ( i.e., the conditions of the Falck-Hillarp method). This fluorescence intensity was nearly twice as high as that obtained from noradrenaline and dopamine under the standard conditions. The results indicate that the acid catalyzes the first step of the histochemical reaction, i.e., the Pictet-Spengler condensation reaction. In this step low fluorescent tetrahydroisoquinolines and tetrahydro-β-carbolines are formed, which are subsequently dehydrogenated to strongly fluorescent products. Low reactive aromatic amines and amino acids, such as phenylalanine, tyrosine, amphetamine and melatonin, gave no or only very low visible fluorescence after this treatment. Thus, the acid-catalyzed histochemical formaldehyde reaction described in this paper exhibits a good specificity for indolylethylamines and 3-hydroxylated or 3-methoxylated phenylethylamines and will also allow the distinction between these structurally related compounds on the basis of their reactivity in the condensation reaction.