In an effort to compare the role of a monofunctional nitrogen mustard with that of its bifunctional counterpart (i.e.,β-CNA, lb) in modulating nonequilibrium activity of opioid receptors, we have synthesized and tested N-(2-chloroethyl)-N-methylamino analogues 2a and 2b. Compound 2b and β-CNA (lb) possessed qualitatively similar pharmacologic profiles on the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Moreover, the corresponding epimer 2a behaved somewhat like that reported for a-CNA (la) in that it possessed irreversible agonist activity in the GPI. The similar pharmacologic profiles of the monofunctional and bifunctional nitrogen mustards suggest that possible cross-linking of receptor nucleophiles by the latter is not critical for activity. In addition, the results are consistent with the idea that the rank-order nonequilibrium activity of 2b at different opioid receptor types is related to its relative affinity at those sites rather than to the alkylation step.