In rhesus monkeys, acute administration of levonantradol and nantradol produced signs of CNS depression, including ataxia with body sag, pupil dilation, ptosis, dozing, and reduced responsivity to external stimuli. Neither compound suppressed the morphine withdrawal syndrome; however, both alleviated the chronic abdominal contraction associated with withdrawal. The directly observable effects of these compounds were not antagonized by naloxone. When levonantradol was administered every 6 hours, marked tolerance developed to both the effects of levonantradol and nabilone and THC. No signs of withdrawal were observed when levonantradol injections were abruptly discontinued. When substituted in lieu of codeine under an intravenous drug self-administration procedure, neither levonantradol nor nantradol maintained responding at rates higher than those maintained by their vehicle. Finally, the discriminative effects of levonantradol were not equivalent to those of the narcotics ethylketazocine or etorphine.