Adrafinil, a vigilance enhancing pharmaceutical, was administered to aged dogs for 14 consecutive days at doses of 10, 20, 30, or 40 mg/kg using a crossover design. The effects on spontaneous behavior in a 10-min canine open-field test were systematically recorded every fourth day, starting with day 1 of treatment. The open field tests were given 2 or 10 h following oral administration of capsules containing either adrafinil or lactose, the placebo control. Adrafinil caused an increase in locomotor activity at the three highest doses at both the 2- and 10-h intervals and during both the first (days 1 and 5) and second treatment week (days 9 and 13). Adrafinil also caused a transient increase in directed sniffing. At the highest dose level, adrafinil caused a decrease in urination frequency. The increased locomotion was generally unaccompanied by stereotypical behavior in the test session. There was some variability; a subpopulation of animals showed either no effect, or decreased locomotion. The individual differences were correlated with changes in serum levels of adrafinil 10 h following treatment.