Abstract: We describe the molecular and functional characterization of the C. elegans unc-63 gene, a levamisole resistance locus on chromosome I, which encodes a nicotinic acetylcholine receptor (nAChR) &agr; subunit. The derived amino acid sequence of UNC-63 most closely resembles that of UNC-38, the product of a separate levamisole resistance locus. Using a gfp::unc-63 fusion construct, expression has been detected in muscles (body wall, vulval) and motorneurons of C. elegans. Nuclear injection into Xenopus laevis oocytes of unc-63 cDNA together with lev-1 and unc-29 results in the expression for the first time of a robust functional C. elegans heteromeric nAChR. The EC50 for ACh of the expressed receptor (20 &mgr;M) resembles that of native nematode muscle nAChRs. Nicotine and the anthelmintic drug levamisole are agonists and mecamylamine is an antagonist of this expressed receptor.