Effects of the substituted benzamide, and of oxiperomide on DA receptors and on Da-related behaviors were the object of the study. The benzamides were practically inactive on DA-sensitive adenylate cyclase and on in vitro [3H] spiperone binding (in the absence of sodium ions). However, all of them inhibited in vivo [3H] spiperone binding in various rat brain regions; this in vivo effect was especially apparent in hippocampus and septum. In frontal cortex, the benzamides (with the exception of metoclopramide) produced only a partial inhibition of [3H] spiperone binding. Such inhibition also occurred in the striatum with sulpiride and tiapride. The results suggest that substituted benzamides are DA antagonists due to their ability to inhibit in vivo [3H] spiperone binding. The lack of agreement between in vivo and in vitro tests is also discussed.