We studied the effect of the sulfhydryl reducing agent dithiothreitol on the binding of the angiotensin II agonist [125I][Sar1]-angiotensin II to AT2 receptors in selected brain areas of young (2-week-old) rats. In the inferior olive and the hypoglossal nucleus, angiotensin II binding to AT2 receptors was insensitive to 5 mM dithiothreitol. Conversely, in the ventral and mediodorsal thalamic, medial geniculate, and oculomotor nuclei, the superior colliculus and the cerebellar cortex, incubation with 5 mM dithiothreitol significantly decreased angiotensin II binding to AT2 receptors to about 40% of control. These data suggest that brain AT2 receptors are heterogeneous with respect to their sensitivity to sulfhydryl reducing agents.