Basic pharmacologic evidences have suggested the effects of dihydroergotoxine mesylate (DEM) on neurotransmitters. In its clinical use, however, various therapeutic effects and side effects are observed when the dose is changed, because of the complexity of this compound and the delicate mechanism of neurotransmitters in the brain, especially when modified by aging and vascular lesions.In order to investigate the optimal dose, a double‐blind study in 550 patients with cerebrovascular disorders was carried out at 68 centers under observation by experienced specialists. Dihydroergotoxine mesylate in sublingual tablets, 3 mg daily, and in oral tablets, 6 mg daily, respectively, was given for 12 weeks, and therapeutic effects at those doses were compared by a double‐blind method. In utility ratings for subjective and psychiatric symptoms, the effects in the oral tablet group at a daily dose of 6 mg were significantly superior to those in sublingual tablet group at a daily dose of 3 mg. There was no significant difference between those two groups in the comparison of side effects.These results show that the daily oral administration of 6 mg of DEM is more suitable for the improvement of subjective and psychiatric symptoms due to cerebrovascular disorders than is the daily sublingual administration of 3 mg. These results suggest that, despite much complexity in the neurohumoral transmitter mechanism in the brain, relatively simple dose‐dependent efficacy of the drug in the range of the therapeutic doses was confirmed for many subjective and psychiatric symptoms of patients with cerebrovascular diso