A new transcranial Doppler system (3-D Transscan, Eden Medizinische Elektronik) was evaluated in relation to sex, age, intersubject, interobserver, side-to-side, and day-to-day variation. Fifty-eight healthy volunteers participated (aged 18-80 yr). Mean velocity was higher in females than in males and decreased with age. The coefficient of variation in the middle cerebral artery was 26% between subjects, 20% between sides, 16% between days, 13% between observers, and 7% during 5 min. The coefficient of variation was higher in the anterior and posterior cerebral arteries. Bruits were heard in 35 subjects, 24 females and 11 males (P = 0.002). When middle cerebral artery velocity was monitored, high- and low-frequency oscillations were found, with a mean frequency of 5 and 1.6/min, respectively. These variations underline the necessity of standardized conditions and very carefully matched control groups in studies using transcranial Doppler. This is especially important when expected changes are small and easy to overlook, as in studies of normal physiological responses and migraine.