The haemodynamic, autonomic and hormonal effects of the centrally acting sympatholytic drug clonidine have been studied in 10 patients with secondary progressive multiple sclerosis (MS) and 10 age- and sex-matched normal subjects (controls). Detailed physiological studies, previously described in these 10 MS patients, indicated that none had postural hypotension or an abnormal Valsalva manoeuvre; six, however, had impaired responses to a range of pressor tests, suggestive of a central autonomic abnormality. In the controls after clonidine, there was a fall in blood pressure and superior mesenteric artery vascular resistance. Finger temperature and growth hormone levels rose. In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process. The impaired growth hormone response to clonidine occurred in a greater number of patients and may indicate lesions in the hypothalamus. These observations in MS patients, without overt clinical evidence of autonomic failure, indicate that the haemodynamic and growth hormone responses to clonidine may be an early indicator of autonomic dysfunction involving central autonomic centres and pathways.