Accelerometry by means of body-mounted piezoresistive sensors was evaluated as a new method to quantify physical activities (body posture and physical and locomotor activity) in relation to the sedative and cardiovascular effects of benzodiazepines, in an ambulatory study. In a double-blind, randomized, crossover study, 12 healthy men received either an oral dose of 2 mg lorazepam, 0.5 mg alprazolam, 1 mg alprazolam, or a placebo on 4 different days. By means of a portable digital recorder, each day 4 hours of continuous measurements of accelerometer signals and heart rate were performed in a living room in the hospital. Changes in subjective sleepiness were assessed at the beginning, halfway, and at the end of the recording period. A separate validation study of the ambulatory environment was performed in three subjects, in which computer classification of activities based on accelerometry was compared with visual evaluation of simultaneously recorded videotapes. In our validation study, comparison of the computer classification with visual analysis based on videotapes revealed an overall agreement for spontaneous and standardized activities of 88% and 96%, respectively. In our pharmacological study, the subjects spent more time in the lying position (p < 0.01) and less time in the sitting position (p < 0.01) after benzodiazepine administration; the effects were strongest for lorazepam. Motility during static activities was reduced (p < 0.025), with motility after lorazepam administration being lowest. Both lorazepam and alprazolam (0.5 and 1 mg) increased subjective sleepiness (p < 0.01). On average , lorazepam induced an overall increase in mean heart rate of about 6%, whereas alprazolam reduced mean heart rate by 2% versus placebo (p < 0.01); the effects were not dependent on posture. The validation study showed that accelerometry forms a reliable method to quantify aspects of normal daily activities. Our pharmacological study revealed that quantification of body postures, physical activity, and motility by means of ambulatory accelerometry proves to be an objective and promising tool to evaluate the psychological and cardiovascular effects of (psycho) pharmaca in relation to the postural and mobility activities of normal daily life.