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The effects of clonidine, rilmenidine, and guanfacine were studied in the holeboard and elevated‐plus maze tests in rats. In the holeboard test, clonidine had a profound effect on locomotor activity, significantly ( P  < 0.05) reducing this measure at all but one of the doses tested (0.005–0.25 mg/kg). In contrast, rilmenidine and guanfacine only markedly affected locomotor activity at 2.5 mg/kg or higher. The ED50<apos;s for locomotor activity were as follows: clonidine, 0.024 mg/kg; rilmenidine, 1.92 mg/kg; and guanfacine 1.65 mg/kg. All three compounds also caused significant decreases in the number of head dips and time spent head‐dipping. The effects of clonidine (0.005–0.25 mg/kg)and rilmenidine (0.25–10 mg/kg)on the number of head‐dips were significant ( P  < 0.01) at all doses and were dose dependent. The actions of guanfacine were similar, with all doses (0.125–5 mg/kg) differing significantly ( P  < 0.05) from the controls, except 1 mg/kg. However, the time spent head‐dipping was only decreased significantly ( P  < 0.05) by clonidine (0.005–0.25 mg/kg), rilmenidine (1,5, and 10 mg/kg), and guanfacine (0.5–5.0 mg/kg). In the elevated plus‐maze, clonidine had no significant effect on the % number of entries made onto open arms, or the % of time spent on the open arms; rilmenidine reduced the % time spent on the open arms, but this decrease was secondary to the drop in total activity; in contrast, guanfacine reduced both the % number of entries made onto open arms and the % time spent on the open arms, and this was independent of the drop in total arm entries, thus indicating an anxiogenic‐like effect. The results show that all three compounds are sedative (as judged by reductions in locomotor activity in the holeboard), with clonidine being much more potent on this measure. Guanfacine differed from the other two compounds in its apparent anxiogenic‐like effects in the plus maze.

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