The effect that chronic unpredictable stress had on the anxiety-like response elicited by the cannabinoid receptor agonist HU-210 [3-(1,1-dimethylheptyl)-(-)-11-hydroxy-delta8-tetrahydrocannabinol] in the elevated plus maze was investigated here. Male Long–Evans rats were either unstressed or were subjected to a 21-day regimen of chronic unpredictable stress, and subsequently were subdivided into three testing groups (vehicle, 10 and 50 μg/kg of HU-210) and tested on the elevated plus maze. Results demonstrated that in unstressed animals, a low dose of HU-210 induced an anxiolytic response, whereas a high dose induced an anxiogenic response. Further, in stressed animals both the low and the high doses of HU-210 induced anxiogenic responses. These findings suggest that chronic stress enhances either cannabinoid receptor responsivity or one of the interacting systems implicated in emotional states.