Thirty patients with essential hypertension (supine diastolic blood pressure 100 to 115 mm Hg) were treated in a randomized, double-blind study with either pindolol (mean dose 28 +/- 5 mg twice a day) or methyldopa (673 +/- 158 mg three times a day) for 12 weeks after a 3-week, single-blind placebo period. In 17 pindolol-treated patients mean supine blood pressure was 163 +/- 3/106 +/- 1 during the placebo period and 155 +/- 3/99 +/- 2 mm Hg (p less than 0.01) during the high-dose period. In 13 patients treated with methyldopa mean supine blood pressure fell from 160 +/- 4/104 +/- 1 to 156 +/- 5/97 +/- 2 mm Hg. Mean standing heart rate was reduced during pindolol therapy from 84 +/- 2 to 79 +/- 2 bpm (p less than 0.05) but was unchanged during methyldopa treatment. Mean supine pretreatment plasma norepinephrine fell from 379 +/- 40 to 337 +/- 33 pg/ml in patients on pindolol therapy and from 448 +/- 76 to 223 +/- 39 pg/ml (p less than 0.02) in the methyldopa-treated group. Although norepinephrine generally decreased in pindolol responders and not in nonresponders, changes in supine diastolic blood pressure and supine plasma norepinephrine did not correlate. In contrast, norepinephrine declined consistently in methyldopa-treated patients regardless of the blood pressure response; changes in diastolic blood pressure and norepinephrine correlated (r = 0.59; p less than 0.05). The results suggest that suppression of sympathetic nervous system activity may play a role in the hypotensive effect of both pindolol and methyldopa.