Male and female rats were exposed to Cannabis smoke or placebo once every second day for 32 days. Following these 16 trials all animals were injected once intraperitoneally with 4 mg/kg THC. After every third inhalation trial and after the injection the rats were placed on a movement sensor for 3 min. Cannabis smoke significantly reduced activity, relative to baseline scores, during the first 10 inhalation trials but by the thirteenth exposure, tolerance was evident. When the animals were injected with THC, the male rats who had been exposed to Cannabis smoke significantly increased their activity whereas the females did not alter their activity relative to the last inhalation trial. In contrast rats of both sexes that had been exposed to placebo smoke significantly decreased their activity following the injection. This intermodal cross-tolerance is discussed in terms of the role of conditioning in the development of tolerance.