The efficacies of an 2-agonist clonidine and an 2-antagonist mianserin were compared in two treatment groups, common migraine and tension headache sufferers. Forty patients entered this double-blind placebo-controlled study. Placebo, clonidine 0.150 mg, and mianserin 30 mg were each administered for 90 day periods. Headaches were induced by intravenous doses of histamine dihydrochloride. The histamine threshold in the common migraine group was significantly lower than in the tension headache group. In the common migraine group, mianserin decreased headache frequency. In the tension headache group, at 90 days mianserin significantly decreased headache intensity and headache frequency. Clonidine significantly decreased headache intensity at 90 days in the common migraine group. At 90 days, mianserin had significantly reduced the Hamilton Depression Rating Scale (HDRS) mean total score, (in the tension headache group), HDRS mean anxiety cluster scores (in both groups), and the HDRS mean depression cluster score (in the tension headache group). At 90 days, clonidine had significantly reduced the HDRS mean total score (in the tension headache group) and HDRS mean anxiety cluster scores (in both groups).