In pithed rats, the H3 agonist R-(-)-alpha-methylhistamine (R alpha MeHA) inhibited the electrically induced increase in blood pressure without affecting the vasopressor response to exogenous noradrenaline. The effect of R alpha MeHA was not affected by the H1 and H2 antagonists dimetindene and ranitidine, but attenuated by the H3 antagonist thioperamide. At higher doses, R alpha MeHA itself increased basal blood pressure; this effect was not affected by the H1, H2 and H3 antagonists. In conclusion, the neurogenic vasopressor response can be modulated via H3 receptors, probably located presynaptically on postganglionic sympathetic nerve fibres.