The type of opioid receptors involved in the conditioned enhancement of natural killer (NK) cell activity is identified in the present study. In our previous observations, we have demonstrated that the conditioned enhancement of NK cell activity was dependent on β-endorphin and methionine-enkephalin, but not dynorphin. Based on the interaction of opioids with their homologous receptors, we concluded that μ- and δ-opioid receptors might be involved. To further classify the type(s) of opioid receptors involved in eliciting the conditioned NK cell activity, three opioid receptor antagonists, cyprodime hydrobromide, ICI-174 844, and nor-binaltorphimine dihydrochloride, were used to block the conditioned NK cell activity in BALB/c mice. Blocking was conducted by intracistemal injection of the drugs. The results showed that the activation of μ-opioid receptors was required in the conditioned enhancement of NK cell activity, but not the δ- or κ-type of receptors.