Using ultrastructural and histofluorescence methods, we investigated the uptake mechanism of catecholamines by the nerve terminals in the cutaneous smooth muscles of stump-tailed macaques (Macaca arctoides). This in vivo approach ultilized the observed cytotoxic effects of 6-hydroxydopamine on these catecholamine-containing terminals and the protective effects of simultaneous treatment with catecholamines (dopamine, norepinephrine, and epinephrine), their 3-0-methylated derivatives (metanephrine and normetanephrine), and catechol acids (3,4-dihydroxymandelic acid and 2, 4, 5-trihydroxymandelic acid). Both catecholamines and 3-0-methylated derivatives protected these nerve terminals from destruction by 6-hydroxydopamine, but catechol acids did not. However, the 3-0-methylated derivatives were less effective than the catecholamines. The degree of protection afforded by these amines depended largely on their concentration. Only catecholamines intensified the electron density of the intravesicular mass or the fluorescence in the nerve terminals; therefore, 3-0-methylated derivatives may inhibit 6-hydroxydopamine uptake at axoplasmic membrane sites, but not inside the axon. These observations led to the discovery that these are two sites for the catecholamine uptake process. One site is the axoplasmic membrane. The terminals are protected by catecholamines and their 3-0-methylated derivatives from 6-hydroxydopamine uptake and thus destruction. The other site is the intraaxonal compartments. Here competitive binding between the vesicular protein and both 6-hydroxydopamine and the catecholamines plays a main role.