Type II procollagen mRNAs are alternatively spliced: type IIA mRNA contains an exon encoding a cysteine-rich domain in the amino-propeptide and type IIB mRNA lacks this exon. In mouse embryos between 9.5 and 13.5 days, type IIA mRNA was the major form of Col2a-1 transcript expressed in both prechondrogenic and nonchondrogenic tissues and type IIB mRNAs were present in small amounts. After 12.5 days, type IIB mRNA levels increased rapidly and finally exceeded type IIA mRNAs. Type IIB mRNAs became the major Col2a-1 transcript by 14.5 days, predominantly expressed in maturing chondrocytes. By 17.5 days type IIB mRNAs account for 80% of the Col2a-1 transcripts. Expression of type IIA mRNAs follows the change in the growth pattern of the cartilaginous model of the axial and appendicular skeleton and of the otic capsule and nasal septum. In nonchondrogenic tissues, type IIA mRNAs are more commonly expressed in epithelial structures of ectodermal and endodermal origin than in nonepithelial tissues. The switching of expression from type IIA to type IIB mRNA as major Col2a-1 transcript may be associated with the commitment of precursor cells to the chondrocyte lineage and sites of type IIA mRNA expression may mark regions of potential cartilage growth. The differential expression pattern of type IIA mRNAs therefore points to an association of type IIA procollagen with chondrocyte differentiation during cartilage growth and some function early in embryogenesis in the epithelial organization of nonchondrogenic tissues.