1. We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic vasculature into extravascular spaces. 2. Splenic arterial infusion of ADM (1, 3 and 9 ng min(-1); n = 9, 11 and 10, respectively) caused a dose-dependent increase in intrasplenic fluid efflux (+0.6 +/- 0.3 (saline) vs. +2.0 +/- 0.3 ml min(-1) (9 ng min(-1) ADM), P < 0.05), and in splenic (venous minus arterial) haematocrit (+0.8 +/- 0.1 (saline, n = 6) vs. +3.1 +/- 0.3 % (9 ng min(-1) ADM, n = 7), P < 0.05). There was no change in splenic weight (0.99 +/- 0.02 (saline, n = 6) vs. 0.99 +/- 0.02 g (9 ng min(-1) ADM, n = 7), P > 0.05). 3. There was no change in MAP before (97.5 +/- 2.2 mmHg), during (98.4 +/- 3.4 mmHg), or after (100.2 +/- 2.2 mmHg) intrasplenic infusion of ADM (9 ng min(-1)) (n = 11, P < 0.05). 4. ADM (9 ng min(-1)) caused an increase in intrasplenic microvascular pressure (11.3 +/- 0.3 (saline, n = 5) vs. 13.0 +/- 0.3 mmHg (9 ng min(-1) ADM, n = 6), P < 0.05). 5. ADM (1 x 10(-11) to 1 x 10(-6) M) induced greater vasorelaxation of isolated preconstricted splenic resistance arteries than veins (maximal relaxation: 60 +/- 0.9 (artery, n = 9) vs. 43 +/- 1.7 % (vein, n = 8), P < 0.05). L-NMMA (10(-4) M) partially inhibited the ADM-induced relaxation in splenic arteries (maximal relaxation: 38 +/- 3 (ADM + L-NMMA, n = 5) vs. 60 +/- 3 % (ADM + D-NMMA, n = 5), P < 0.05). 6. It is concluded that ADM increases fluid efflux from the splenic vasculature by differentially reducing pre- vs. post-capillary resistance, thus increasing intrasplenic microvascular pressure.