Specific agonists and antagonists for alpha 1- and alpha 2-adrenoceptors were used to determine an alpha-adrenoceptor-mediated action of adrenaline on the rate of sterol synthesis from [14C]acetate in freshly isolated human mononuclear leukocytes. In the presence of the beta-adrenergic blocker propranolol (1 microM), adrenaline (100 microM) and noradrenaline (100 microM) suppressed sterol synthesis by 36% and 38%, respectively, suggesting an action via alpha-adrenoceptors. The catecholamine effect could be mimicked by alpha 2-selective beta-phenethylamines including alpha-methylnoradrenaline, but not by imidazolines. alpha 1-Selective agonists like phenylephrine and methoxamine had no effect on the pathway. Accordingly, the effects of adrenaline and the alpha 2-selective agonist alpha-methylnoradrenaline on sterol synthesis were attenuated by the unselective alpha-antagonist phentolamine and the selective alpha 2-antagonist yohimbine, but not by the alpha 1-antagonist prazosin. The results provide evidence that catecholamines can affect sterol synthesis in human mononuclear leukocytes by stimulating alpha-adrenoceptors of the alpha 2-subtype.