The contractile response of isolated rabbit aorta rings to 5-hydroxytryptamine (5-HT) was antagonized by spiperone and four other butyrophenone analogs in a competitive manner. The Kb values were (nanomolar):spiperone, 0.8; spirilene , 2.1; benperidol , 4.4; azaperone, 16.6; and haloperidol, 96.6. The Kd values for four of these drugs, whose affinities for [3H]ketanserin and [3H]spiperone binding sites in rat brain membranes have been measured, are almost indistinguishable from the Kb values in inhibiting 5-HT-induced contraction of the rabbit aorta. This suggests a congruence between the aortic "D" receptors and 5-HT2 type binding sites in rat brain. Among the drugs we tested, one portion of the molecule is almost identical; the other portion of the molecule differs in four of the five compounds. It is suggested that their rank order as antagonists of the 5-HT receptor in the aorta depends on the degree of recognition of the nonbutyrophenone part of the molecules by the receptor.