1 The specific histamine H2-receptor agonist, impromidine (3-100 nmol/l), increased the rate and force of beating of guinea-pig isolated atria. These effects were blocked by the H2-receptor antagonist, cimetidine (30 Mmol/l), but not by the Hi-receptor antagonist, mepyramine (0.1 pmol/1). 2 In atria that had previously been incubated in [3H]-noradrenaline, impromidine (3-100 nmol/l) had no effect on the resting efflux of radioactivity, but concentrations of 50 and 100 nmol/l significantly increased the efflux induced by electrical stimulation (2 Hz for 10 s) of the intramural sympathetic nerves by approximately 38%; lower concentrations (3, 10 and 25 nmol/l) had no effect. 3 The effect of impromidine in enhancing stimulation-induced efflux of radioactivity was abolished by cimetidine (30 pmol/l) and by mepyramine (0.1 lmol/l). It was unaffected by the ac-adrenoceptor antagonist, phentolamine (30 pmol/l). 4 Impromidine produced some inhibition of the uptake of [3H]-noradrenaline, but this did not account for the enhancement of the stimulation-induced efflux of radioactivity, since impromidine (50 nmol/l) still increased release in the presence of cocaine (3011mol/l). 5 The specific H,-receptor agonist,2-(2-pyridyl)-ethylamine (10-100 pmol/l), increased both the resting and stimulation-induced efflux of radioactivity. These effects were not blocked by mepyramine (0.1 umol/l) or the P-adrenoceptor antagonist, metoprolol (0.1 gImol/l).6 The prejunctional inhibitory histamine receptors in guinea-pig atria are not classifiable into H1-or H2-type by the use of relatively specific postjunctional histamine H1-or H2-receptor agonists and antagonists.