Cannabinoids are currently used for the treatment of excessive weight loss and nausea; however, there are very few studies that have examined cannabinoid effects in females of any species. A previous study has shown that there are sex differences in cannabinoid pharmacokinetics in rats, suggesting that there could be sex differences in cannabinoid-induced behaviors. To address this issue, Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol (natural cannabinoids) or (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) (CP55940, a synthetic cannabinoid) was administered i.p. to male and female Sprague-Dawley rats, who were tested on the 50 degrees C warm water tail withdrawal, paw pressure, catalepsy bar and spontaneous locomotor activity tests at various times post-injection. At the doses tested, all three cannabinoid agonists produced greater effects in females than males in two or more behavioral tests. This study demonstrates that there are sex differences in the behavioral effects of cannabinoids in the rat.