Twelve healthy subjects with no history of substance abuse participated in a placebo-controlled single-blinded study of subjective response to acute i.v. administration of placebo and two doses of the natural shortened peptide sequence of the kappa-opioid agonist, dynorphin A(1-13) (low dose 120 micrograms/kg, high dose 500 micrograms/kg). Visual analog scales showed small but significant negative mood and positive drug effect 10 min post infusion in the high dose dynorphin compared to placebo infusion. The differences were no longer apparent at 30 min. These results show that dynorphin A(1-13), shown previously to have both neuroendocrine and modest analgesic effects, was well tolerated and produced modest transient subjective responses.