In a dose-response study of prazosin in 24 patients with Raynaud's phenomenon, the clinical effectiveness and side effects of 3, 6, and 12 mg prazosin administered daily were compared. Diary analysis and measurement of finger skin blood flow and temperature before, during, and after cold challenge showed no major differences among these three dose regimens. Standing systolic blood pressure decreased significantly during the 12-mg period in comparison with the 6-mg (P less than .05) and with the 3-mg period (P less than .02), whereas heart rate increased in the 6-mg and 3-mg periods (P less than .05). In the higher dosage ranges, spontaneous mentioned side effects were noticed most often, which was in accordance with the results of a checklist analysis on adverse effects. Three patients withdrew from the study because of complaints that might be due to orthostatic hypotension. Most patients that wanted to continue prazosin after this study (n = 13) did so on a 3-mg basis (n = 10). Because prazosin 3 mg daily is more effective in treating of Raynaud's phenomenon than is placebo, the study shows that in a dosage of 3 mg daily, the best balance between clinical effectiveness and side effects is obtained.