BACKGROUND In order to facilitate direct comparisons of anticholinergic drug effects on activity, nine drugs were tested in one laboratory using a standardized procedure. OBJECTIVE The present study compared the effects of aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide, and trihexyphenidyl hydrochloride on activity levels in rats. METHODS Both fine motor activity (reflecting smaller movements) and ambulatory activity (reflecting larger movements) were recorded for 23 h following drug administration in food-restricted rats. All drugs were administered during the light period of the photocycle. RESULTS Atropine, azaprophen, biperiden, scopolamine, and trihexyphenidyl increased both ambulations and fine motor activity significantly during the first hour post-injection, but the increased activity levels returned to vehicle control levels within 2-6 h post-injection. Benactyzine and procyclidine only increased fine motor activity significantly above vehicle control levels and activity levels returned to vehicle control levels within 2-3 h. Finally, aprophen and diazepam generally did not increase measures of activity significantly above vehicle controls at the dose ranges examined. CONCLUSIONS Based on potencies relative to scopolamine, the potency of the drugs could be ranked as follows: scopolamine > trihexyphenidyl > biperiden > azaprophen > procyclidine > benactyzine > atropine > aprophen. The comparison of drug effects on activity may be useful in selecting anticholinergic drug therapies with a minimal range of side effects. In addition, these data may reduce the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests.