Although several reports suggest that bee venom may be an effective treatment for patients with multiple sclerosis (MS), patients may be subjected to real risks of serious allergic reactions as well as emotional and economic costs. This study was conducted to evaluate the safety of bee venom extract as a possible treatment for patients with progressive forms of MS. A total of nine bee venom nonallergic patients with progressive forms of MS, who were 21-55 years of age with no other illnesses, were entered into four groups (A, B, C, and D) on a structured 1-year immunization schedule. Hyperreactivity to bee venom was evaluated by questionnaire, physical examination, and a battery of hematologic, metabolic, and immunologic tests. Responses to therapy were evaluated by questionnaire, functional neurological tests, and changes in measurement of somatosensory-evoked potentials. Although no serious adverse allergic reactions were observed in any of the nine subjects, four experienced worsening of neurological symptoms, requiring termination in the study; this could not be ascribed to side effects of the therapy. Of the remaining five subjects, three felt that the therapy had subjective amelioration of symptoms and two showed objective improvement. Although this preliminary study suggests safety, because of the small numbers studied, there were no definite conclusions regarding efficacy and therefore there was little evidence to support the use of honeybee venom in the treatment of MS. Larger and more carefully conducted multicenter studies will be required to establish efficacy.