The present study was undertaken to investigate the effects of adrenomedullin (ADM), a newly discovered peptide in normal human plasma, in the pulmonary and systemic vascular bed of the intact cat. Because pulmonary blood flow and left atrial pressure were held constant, changes in lobar arterial pressure directly reflected changes in pulmonary vascular resistance. Under conditions of resting (low) pulmonary vasomotor tone, intralobar arterial bolus injections of ADM-(1-52) and two truncated ADM sequences, ADM-(13-52) and ADM-(1-12), had little effect on baseline lobar arterial pressure. In contrast, when pulmonary vasomotor tone was actively increased by intralobar arterial infusion of U-46619, intralobar arterial bolus injections of ADM-(1-52) (10-3,000 ng) and ADM-(13-52) (10-3,000 ng) decreased lobar arterial pressure in a dose-dependent manner, whereas only the highest doses of ADM-(1-52) and ADM-(13-52) (1,000-3,000 ng) mildly decreased systemic arterial pressure. Under the same experimental conditions, injections of ADM-(1-12) had no effect on lobar arterial and systemic arterial pressures. The present data suggest that ADM-(13-52) or a similar ADM fragment is responsible for the marked pulmonary vasodilator activity of ADM-(1-52) in vivo.