1. OPC-21268 and OPC-31260 are newly developed orally active non-peptide vasopressin (AVP) V1 and V2 receptor antagonists, respectively. The effects of the two compounds on human vessels have not been studied. 2. The effects of the two compounds on AVP-induced contraction of human internal mammary arteries (IMA) were investigated. Their effects were compared with the peptide V1 and V2 antagonists d(CH2)5Sar7AVP (SAVP) and d(CH2)5D-Ileu2Ileu4AVP (Ileu2Ileu4AVP), respectively. 3. The V1 antagonist OPC-21268 failed to antagonize AVP-induced contraction at low concentrations and potentiated the contraction at higher concentration (3 x 10(-7) mol/L, P < 0.05). It also caused a mild direct contractile effect on IMA. In contrast, the peptide V1 antagonist SAVP potently inhibited the AVP-induced contraction, indicating that functionally constrictor V1 receptors exist in IMA. Both the nonpeptide and peptide V2 antagonists OPC-31260 (3 x 10(-6) mol/L) and Ileu2Ileu4AVP significantly antagonized the AVP-induced contraction (P < 0.01). 4. The AVP-induced contraction was reversed by high concentrations of OPC-31260 (10(-6) mol/L-3 x 10(-5) mol/L) but not by OPC-21268 (up to 3 x 10(-5) mol/L). 5. These studies indicate that, in human IMA, OPC-21268 is a partial V1 receptor agonist with no V1 receptor antagonist activity, while OPC-31260 is a V1 receptor antagonist. The results also indicate that Ileu2Ileu4AVP may be a V1 receptor antagonist in humans.