The clinical features of progressive supranuclear palsy (PSP) overlap with other parkinsonian syndromes, including multiple system atrophy (MSA). Autonomic dysfunction is a characteristic of MSA, but has also been described in PSP. We therefore report results from a series of physiological studies of cardiovascular autonomic function in 35 PSP and 20 MSA subjects, and 26 age-matched healthy control subjects. The response to growth hormone-clonidine testing, a neuropharmacological assessment of central adrenoceptor function, was also assessed in 14 PSP and 10 MSA subjects, and compared with 10 controls. None was on medication which may have affected the results. Orthostatic hypotension did not occur in PSP subjects or controls, unlike MSA subjects. Overall there was no evidence of sympathetic vasoconstrictor failure in PSP subjects, unlike MSA subjects, although the pressor response to mental arithmetic was reduced. Cardiac parasympathetic function was affected in only a minority (three of 35) of PSP subjects and was abnormal in MSA subjects. After clonidine administration, growth hormone rose in PSP subjects (median increase 4.3; interquartile range 1.8-7.8 mU/l) and controls, unlike MSA subjects (0.9; 0.3-2.4 mU/l; P < 0.005, Mann-Whitney U-test). In conclusion, in PSP subjects, responses to both physiological and pharmacological tests provided evidence against widespread autonomic dysfunction; this differed markedly from MSA subjects. Thus, cardiovascular autonomic dysfunction should be an exclusionary feature in the diagnosis of PSP.