In Wistar rats, an increase in renal sympathetic activity is induced by activation of presympathetic neurones in the paraventricular nucleus (PVN) and reflexly by a mild venous haemorrhage. Both stimuli are dependent on the release of vasopressin and glutamate at spinal synapses. The significance of the supraspinal pathway and the co-operative interaction of vasopressin with an excitatory amino acid is unclear. The present study examines this in Brattleboro rats, which have a natural vasopressin gene deletion. The responses were compared with Long-Evans rats, from which Brattleboro rats are derived. All rats were anaesthetized with a mixture of urethane (650 mg kg(-1) i.v.) and chloralose (50 mg kg(-1) i.v.). Recordings were made of blood pressure, heart rate and renal sympathetic nerve activity (RSNA). Microinjection of d,l-homocysteic acid (DLH, 0.2 m, 100 nl) at sites restricted to the PVN elicited significant increases in RSNA (P < 0.001) in both strains of rats. These changes were significantly reduced (P < 0.01) in Long-Evans rats by intrathecal application to the spinal cord of either a V(1a) antagonist or a glutamate antagonist (kynurenic acid), whereas in Brattleboro rats the changes were significantly reduced (P < 0.05) only by kynurenic acid. Removal of 1 ml of venous blood in Long-Evans rats increased RSNA by 28 +/- 4% (P < 0.01), which was significantly reduced (P < 0.05) by prior intrathecal application of either the V(1a) antagonist or by kynurenic acid. The same test in Brattleboro rats caused a significantly greater (P < 0.05) increase (63 +/- 14.7%) in RSNA which, in contrast to Long-Evans rats, was unchanged by intrathecal application of the V(1a) antagonist, being significantly reduced (P < 0.01) only by intrathecal kynurenic acid. Thus, in Brattleboro rats, the lack of vasopressin in the brain sympathetic pathways appears to be compensated, acutely, by glutamate-releasing pathways. This might indicate that, in normal rats, vasopressin is more important in maintaining longer term adjustments to stressors.