Members of the Id family of helix-loop-helix proteins are ubiquitously expressed and dimerize with members of the class A and class B basic helix-loop-helix proteins. Due to the absence of a basic region, Id proteins act as dominant-negative antagonists of basic helix-loop-helix transcription factors, which regulate cell growth and differentiation in diverse cell types. Recent findings suggest that the functions of Id proteins are well regulated at both the transcriptional level and the post-transcriptional level. We show here that the alternative splicing variant of human Id-1 protein possesses a different binding specificity for basic helix-loop-helix transcription factors and is expressed in a cell cycle-dependent manner. Therefore, alternative splicing of Id-1 could provide a post-transcriptional mechanism to regulate Id-1 function.