We isolated and sequenced genomic and cDNA clones encoding the complete amino-terminal portion and the 5'-untranslated region of mouse pro-alpha 2(XI) collagen mRNA. Fourteen exons encoded the amino-terminal propeptide, which was divided into three consecutive domains (a long globular domain, an amino-terminal triple helical domain, and a telopeptide domain). The long globular domain was further divided into an upstream basic subdomain and a downstream highly acidic subdomain, as is the case for the amino-terminal propeptides of pro-alpha 1(V) and pro alpha 1(XI) collagens. We also demonstrated that the primary transcript undergoes complex alternative splicing. Three consecutive exons (exons 6, 7, and 8) encoding most of the acidic subdomain showed alternative splicing which dramatically affected the structure of the amino-terminal propeptide of pro-alpha 2(XI) collagen. Using the reverse transcription-polymerase chain reaction, we analyzed the expression of these exons in various tissues and in developing limb buds of mice. The pro-alpha 2(XI) transcripts were abundant in cartilage, but most of them lacked the 3-exon sequences encoding the acidic domain. Most of other tissues also contained mRNAs that corresponded to longer splice variants, including exons 6-8. The differential expression of specific domains of pro-alpha 2(XI) collagen may be important in modulating interactions between various components of the extracellular matrix and/or may influence heterotypic collagen assembly.