Central and systemic morphine analgesia as well as both opioid and nonopioid forms of swim analgesia display gender differences with male rats showing greater magnitudes of analgesia than female rats. Since nonopioid swim analgesia is dependent upon muscarinic cholinergic and alpha 2-noradrenergic mechanisms, the present study evaluated in rats whether gender, adult gonadectomy or estrous phase altered analgesia induced by either the muscarinic cholinergic receptor agonist, pilocarpine or the alpha 2-noradrenergic receptor agonist, clonidine. Pilocarpine (1-10 mg/kg) analgesia was significantly greater in male rats. Female rats displayed 7-fold and 3-fold rightward shifts in peak analgesia on the tail-flick and jump tests respectively. Clonidine (100-500 micrograms/kg) analgesia was significantly greater on both nociceptive tests in males, but only produced a 2-fold rightward shift in peak analgesia in females on the jump test. Whereas castration failed to shift either dose-response curve, ovariectomy mitigated the gender differences in pilocarpine and clonidine analgesia. Both pilocarpine and clonidine analgesia were not altered by estrous phase changes. These data indicate that gender differences in analgesia are not specific to opioid systems.