The phylogenic conservation of the proto-oncogene c-fos suggests that this gene product is required for normal metabolic processes. Investigations into the transcription pattern of c-fos in normal tissues and cells^1–8 have revealed expression during development, differentiation and growth^1,3–7 which is dependent to a large extent on external signals transferred by growth factors^9–15. The complex pattern of stage and tissue-specific expression has raised the hypothesis that the c-fos gene product might function in the control of either proliferation or differentiation^7,16. However, no detailed analysis is yet available concerning the normal expression of c-fos during embryonic and fetal development. Interestingly, recent data derived from studies in transgenic mice reveal that the biological effect of overexpression of exogenous fos is restricted to the developing bone tissue and T-cell development of the mice, perhaps signifying that these cells represent a physiological target tissue of the proto-oncogene fos¹⁷. Thus, to gain deeper insight into the functional role of the c-fos gene product during physiological processes, it is a requirement to carry out a detailed analysis of the localization and cell-type specificity of c-fos expression in normal mouse embryos. Using the technique of in situ hybridization, we demonstrate here that stage-specific expression of the proto-oncogene c-fos in mouse embryos is restricted to the peri-chondrial growth regions of the cartilaginous skeleton. Moreover, we found strong c-fos transcription in web-forming mesodermal cells, which are also characterized by a stage-specific high growth capacity. Our results suggest a tissue-specific regulatory role of c-fos during differentiation-dependent growth processes of fetal bone and mesodermal web tissue.