Using the monoclonal antibody MZ15 in immunocytochemical and ultrastructural studies we have been able to determine the spatiotemporal pattern of keratan sulfate (KS) distribution during quail craniofacial morphogenesis. KS-containing proteoglycans are found associated with invaginating placodes (olfactory, lens and otic), in developing pronephric tubules, notochord, pharynx and endocardium, and display developmental regulation. The appearance of such proteoglycans (PGs) during placode morphogenesis is particularly striking and we suggest that they may be an important component of the extracellular matrix which has been previously implicated in mediating the morphogenetic interactions and cell movements occurring at these sites. The otic vesicle during stage 18-22 displays a notable asymmetric distribution of KS-containing PGs. The role that these molecules may play and the reasons for this regionalization are, as yet, unclear but it is conceivable that the distribution of proteoglycans at this stage reflects subsequent differentiative events during otocyst development. Furthermore, our ultrastructural observations indicate that over the developmental period studied (H & H stages 8-22) keratan sulfate exists in at least two proteoglycan forms. Some spatiotemporal correlation has been found to exist between the distributions of KS-containing PGs and type II collagen as previously reported by Thorogood et al. (1986). We suggest that the proteoglycan detected at such sites is cartilage-specific proteoglycan and that it plays an important role, together with type II collagen, in the "signalling" mechanism which specifies the subsequent pattern of the chondrocranium. It is proposed that this interaction at epithelio-mesenchymal interfaces in the developing head parallels the matrix-mediated tissue interaction between notochord and somites which results in the formation of the cartilaginous primordia of the vertebrae from the sclerotomes as reported by Lash and Vasan (1978).