We have isolated and determined the nucleotide sequence of a cDNA clone that contains the entire coding sequence of human calmodulin and substantial parts of the untranslated flanking regions of the mRNA. This clone was detected serendipitously in the course of screening a cDNA library with a mixture of oligodeoxyribonucleotide probes based on a target amino acid sequence from an unrelated protein. The predicted primary structure of the translation product of the calmodulin mRNA is identical with that determined for calmodulin from human brain by direct amino acid sequence analysis except for the presence of an additional methionine residue at the N-terminus which appears to be the site of initiation.