The ETA receptor antagonist, BQ 123 was used to characterize depressor and initial and delayed pressor responses to ET-1 in conscious rats. BQ 123 (0.001-0.01 mumol/kg/min) dose-dependently inhibited the initial ET-1 (0.1 nmol/kg) pressor response, reaching a maximum after 0.01 BQ 123 (61 +/- 4% inhibition). Less inhibition of the pressor effects occurred after higher doses of BQ 123 (1: 10 +/- 6% inhibition). The depressor response to 1 nmol/kg ET-1 was unchanged by BQ 123 (0.01), but inhibited by BQ 123 (1). The initial pressor response to 1.0 nmol/kg ET-1 was inhibited by BQ 123 (0.01: 26 +/- 6%; 1.0: 41 +/- 3% inhibition). The delayed pressor response, 180 min post-ET-1 (+41 +/- 2% increase) was reduced by BQ 123 infused before the delayed peak (+14 +/- 5% increase). Plasma immunoreactive ET values were: control: 5.4 +/- 0.4; initial peak: 491.4 +/- 50.6; delayed peak: 8.2 +/- 0.6 fmol/ml. The delayed ET-1 response does not coincide with sustained high circulating levels of immunoreactive ET, but inhibition of the response by BQ 123 suggests that it may involve endothelin receptors.