[D-Pen2, D-Pen5]enkephalin (DPDPE), a selective agonist at delta opioid receptors, causes excessive vertical rearing when given icv to rats or s.c. to mice. Tolerance develops to this behaviour. Rats do not rear excessively when injected icv with the following prototype agonists at opioid receptors: DAGO, dynorphin A, U-50488H or SK&F 10047. The incidence of DPDPE-induced rearing is reduced when rats are pretreated s.c. with ICI 174864 (a selective antagonist at delta opioid receptors) (A50 = 0.09 mg/kg) but not by ICI 178173 (an inactive analogue of ICI 174864); this finding suggests that delta binding sites mediate the behaviour. Pretreatment with naloxone attenuates rearing but the antagonism is unimpressive over the dose range tested (0.05-1 mg/kg, s.c.). Low doses of haloperidol (A50 = 0.05 mg/kg, s.c.) antagonize the rearing. Dopamine may therefore mediate the behaviour through delta receptor modulation of dopamine release. The practical gain from this study is as follows: a simple, discriminating test is now available for evaluating novel delta agonists and antagonists in vivo.