Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE), cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 46 normal subjects, 28 high intestinal tone (high IT) and 18 low intestinal tone (low IT), before and after the administration of a single intramuscular dose of clonidine (2.5 µg/kg). High IT subjects had lower mean values of DBP than low IT subjects, and basal NE was significantly greater in low IT than in high IT subjects. A negative correlation between NE and IT values was found for the high IT, but not for the low IT group, during the preclonidine periods. The drug reduced SBP in high IT, whereas it reduced SBP plus DBP and NE in low IT subjects. Clonidine induced significant reductions of CRT and increases of GH in both groups; furthermore, a slight but significant reduction of PRL was registered in high IT group. The drug also induced increase of distal colon tone in high IT subjects and suppressed phasic activity (waves) in low IT subjects. While a significant positive correlation was found between NE and DBP in low IT subjects during postclonidine periods, no correlation was found between the two parameters in high IT subjects. Other significant positive (+) and negative (–) correlations during postclonidine periods were: CRT/GH (–), CRT/PRL (+), and GH/PRL (–) in high IT subjects; NE/CRT (+), NE/GH (–), CRT/GH (–), CRT/DBP (+), and GH/DBP (-) in low IT subjects. Finally, significant negative correlation was found between NE and distal colon tone during postclonidine periods in high IT subjects. Our results suggest that there is a sympathetic (NE) hypoactivity in high IT subjects and a sympathetic (NE) hyperactivity in low IT subjects. Postsynaptic and presynaptic pharmacological mechanisms are postulated in order to explain these two different patterns of responses to the challenge of