The mouse alpha 1(II) collagen gene has been isolated and a 5' portion of the gene which has low homology to other collagen genes was used to study the pattern of expression during mouse embryogenesis. In situ hybridization studies show that in the mouse, like the chick, alpha 1(II) collagen is expressed in chondrogenic tissues in advance of chondrocyte differentiation. The gene is expressed early in embryogenesis at 9.5 days both in the cranial mesenchyme destined for the chondrocranium, and the sclerotome of the somites, and at 12.5 days in the primordia of the hyoid and the laryngeal cartilage. Type II collagen gene transcripts were found in all the chondrogenic tissues of the axial and appendicular skeleton until the onset of endochondral ossification. Expression of alpha 1(II) collagen mRNA was also observed in non-chondrogenic tissues such as the notochord which may be responsible for inducing chondrogenesis in somitic mesoderm, neural retina, the corneal and conjunctival epithelia and sclera of the developing eye. Expression in the tail tendon was late, at 16.5-18.5 days. Transient expression was also found in the heart at 9.5-12.5 days, the epidermis at 10.5-14.5 days, the calvarial mesenchyme at 12.5-16.5 days, the inner ear at 14.5 days and the fetal brain from 9.5-14.5 days. Within the neural tube, alpha 1(II) collagen mRNA was localized in the proliferative ventricular cells of the forebrain and midbrain of 9.5- to 10.5-day embryos. Subsequently, transcription of the alpha 1(II) collagen gene was confined to restricted areas of the rhombencephalic basal plate, the ventricular layer of the hindbrain and the cervical spinal cord. These examples of expression of the type II collagen gene in the developing nervous system seem to suggest that active transcription of this gene might be associated with early stages of neuroblast differentiation. Type II collagen may therefore have additional roles in development unrelated to chondrogenesis.