Activation of opioid receptors has generally been considered to produce inhibitory effects on neuronal activity. However, recent studies indicate that specific mu-, delta- and kappa-opioid receptor agonists can elicit excitatory, as well as inhibitory, modulation of the action potentials of sensory neurons isolated in culture. Stanley Crain and Ke-Fei Shen review the evidence for mediation of these direct excitatory effects by naloxone-reversible opioid receptors. They propose that this dual modulatory mechanism may help to account for previously unexplained enhancement by opioids of transmitter release, paradoxical hyperalgesic and aversive effects of opioids, and some aspects of opioid tolerance and addiction.