Oral administration of difenidol hydrochloride before space flight has become a common practice in China.To evaluate the effects of multiple administration of difenidol on the brain cognitive processing in addition to its role in the prevention of space motion sickness will make it easier for ground monitors to make decision under emergency during the first two or three days of the space flight.We have recruited 20 health volunteers(14 M,6 F,aged 24-38yrs)to participate in this experiment.The experiment was double blind self-controlled design.Three days before experiment they were randomly given first dose of difenidol hydrochloride or placebo(50mg,one capsules).Then they administered capsules three times a day until the onset of experiment.The interval between two experiments was over three days.In the experimental day subjects were asked to lie supine for 30min,-6° tilt for 3h and then recovered for 30min in supine.They were asked to perform cognitive task twice: one trial in supine,one trial in the last 10min of 3h of-6° tilt.The visual cognitive tasks were presented by a laptop.Pairs of bicolored light dot flashed sequentially to produce a perception of movement.Subjects were required to attend selectively to a critical feature of the moving target,e.g.,color or direction.The tasks included: a no response task,a color selective response task,a moving direction selective response task,and a combined color– direction selective response task.It was found that in acute blood redistribution experiments that the reaction time shortened for about 20 to 30ms when performing choice attention task in head-down tilt than in supine position.P3 amplitudes were decreased when performing no response task under headdown tilt not under supine position after diphenidol administration.P3 amplitudes were decreased when performing color selective attention task and increased when performing direction selective choice task.The P3 amplitudes increased in the coaction of diphenidol and blood distribution compared with in supine after diphenidol administration.It was suggested that blood redistribution can speed up the reaction time to choice attention tasks.For feature and space attention,the action of diphenidol was superior to blood redistribution.The central active inhibition was dropped in feature attention and the need for brain resources mobilization was enhanced in space attention.And for higher cognitive load task,the efficacy of brain updating was decreased in combination of diphenidol and blood redistribution.