We have cloned Calx, a gene that encodes a Na-Ca exchanger of Drosophila melanogaster. Calx encodes two repeated motifs, Calx-alpha and Calx-beta, that overlap domains required for exchanger activity and regulation. Calx has multiple transcripts in adults, including at least one expressed in the retina. The Calx genomic locus comprises >/=35 kb between the Atpalpha and rudimentary-like genes in chromosomal region 93B. In Xenopus oocytes, microinjected Calx cRNA induces calcium uptake like that of its homolog, the 3Na+-1Ca2+ exchanger of mammalian heart. Implications of Calx-alpha motifs for the mechanism of Na-Ca exchange are discussed.