In a double-blind placebo-controlled parallel study, we assessed basal and post-therapeutic sympathetic activity both in supine and standing positions in mildly to moderately hypertensive patients by two different methods: frequency domain indices of heart rate variability (HRV) and plasma levels of both noradrenaline (NA) and its metabolite, 3,4-dihydroxyphenylglycol (DOPEG). Patients were evaluated on placebo and after 8 weeks of treatment with either cilazapril, 2.5-5 mg/day (13 patients) or atenolol, 50-100 mg/day (14 patients). Twenty-four-hour blood pressure was similarly reduced (p < 0.01) by both cilazapril and atenolol. Heart rate decreased with atenolol by 14 beats per min (p < 0.001) but did not change with cilazapril. When compared to the placebo, cilazapril did not modify sympathetic activity indices of HRV but did significantly reduce NA and DOPEG levels in both the supine and standing (p < 0.05) positions. As expected, atenolol reduced (p < 0.05) sympathetic activity indices of HRV but did not modify NA levels in either position. Moreover, while on placebo, patients showed no significant correlations between values of NA or DOPEG, nor in any of the HRV indices. We conclude that: (1) the antihypertensive effects of cilazapril and atenolol are similar, but in these patients, sympathetic activity indices showed divergent results both before and after therapy; (2) this may be due to different aspects of sympathetic activators, assessed independently by different methods, and (3) these discrepancies must be taken into account when evaluating autonomous nervous system parameters.