We have synthesized a series of hydrazones and acylhydrazones of naltrexone. These substitutions had modest effects on competition of mu binding but many greatly enhanced the relative potency of the compounds for delta receptors. Increased delta affinity was most prominent with the acylhydrazones. Many of the derivatives elicited a wash-resistant inhibition of binding which was restricted to mu, not delta, binding sites. This wash-resistant inhibition of binding did not correlate with affinity, as determined by IC50 values, implying that the inhibition could not be explained simply by slow rate of dissociation due to increased affinity.