The centrally acting alpha 2-adrenoceptor agonist clonidine was used to assess the sensitivity of alpha 2-adrenergic neurotransmission in man, using receptor-binding studies and clonidine-induced growth hormone response. Neither acute (2 micrograms/kg body weight) nor subchronic (3 days, 2 x 150 micrograms/kg body weight) administration of clonidine affected platelet alpha 2-adrenoceptor number in humans as judged by 3H-yohimbine and 3H-UK-14,304 binding. The same treatment also did not modify central postsynaptic alpha 2-adrenoceptor function in the same individuals as assessed by clonidine-induced growth hormone responses. Similarly, subchronic (3 days, 500 micrograms/kg body weight, i.p.) or chronic (14 days, 500 micrograms/kg, i.p.) administration of clonidine to mice failed to change 3H-yohimbine or 3H-UK-14,304 binding sites in membranes prepared from frontal cortex. On the other hand, in vitro experiments using mouse frontal cortex or human platelet membranes showed pronounced reduction of 3H-UK-14,304 but not of 3H-yohimbine binding sites after incubation with several adrenoceptor agonists. The data indicate that acute and subchronic clonidine treatment may not change alpha 2-adrenoceptor sensitivity in humans or mice as assessed both at the functional and receptor level.