Patients with primary autonomic failure may have either pure autonomic failure (PAF) or multiple system atrophy (MSA) in which there is additional neurological involvement. Distinction between PAF and MSA at an early stage is important because a wide range of complications is associated with MSA, which has a poor response to drug therapy and a less favourable prognosis. We have investigated the growth hormone (GH) releasing effects of clonidine in patients with PAF and MSA to see whether this hormonal response could serve as a neuroendocrine marker to distinguish between the groups. Age-matched normal subjects were studied as controls. Both groups of patients had severe postural hypotension due to primary sympathetic failure of presumed central origin in MSA and peripheral origin in PAF. After clonidine, plasma GH concentrations increased in controls and PAF, with no change in MSA. Changes in plasma glucose and insulin concentrations were similar in all groups. Clonidine, therefore, stimulates growth hormone release in PAF but not MSA and may serve as a neuroendocrine marker in differentiating patients with MSA and a central autonomic defect from those with PAF with a peripheral defect.