BACKGROUND Using transcranial Doppler sonography (TCD), changes in blood flow velocity (BFV) can be measured in the Medial Cerebral Artery (MCA) during cognitive effort. Our goal was to define the time-course and laterality of BFV in healthy volunteers during arithmetic and verbal fluency tasks according to handedness. METHODS Twelve subjects (8 right-handed, 4 left-handed) were assessed. The TCD registered BFV in both MCA simultaneously. Heart rate was also recorded using TCD. Finally we included a 16-channel EEG. BFV laterality index (LI) was calculated. Participants were asked to count silently and generate words beginning with a specified letter. To estimate hemispheric differences in BFV, two-tailed Wilcoxon tests were utilized along with correlational analyses. RESULTS During cognitive effort the BFV changed in a tri-phasic manner in all participants. A 6-8% elevation of BFV was observed in MCAs without latency at the time of the evoking signal. Laterality of BFV developed after 5-13 seconds during cognitive effort in right-, and several seconds later in left-handed subjects. During tasks the BFV increased in the dominant hemisphere up to 2.6-4.7% compared to the subdominant one. We also calculated the LI. During the verbal task the LI agreed with the handedness in 9 out of 12 subjects. During the mental arithmetic task, agreement was found in 6 out of 12 subjects. According to LI results we found a discrepancy between verbal and arithmetic tests in 3 out of 12 subjects. CONCLUSIONS Cognitive effort elicites significant bilateral BFV increases in the MCAs, which suggests fast neurogenic regulation. The course of BFV during mental arithmetic proved to be different from course BFV assessed during the word fluency task. Based on the laterality of the BFV, the word-generation task was more sensitive in determining the dominant hemisphere when compared to the mental arithmetic task. The use of LI may help to estimate hemispheric functions even in pathologic circumstances.