Integrin α1β1 is a collagen receptor predominantly found in mesenchymal tissues. Mice lacking this receptor are viable. We have previously suggested that α1β1 might participate in the down-regulation of collagen gene expression observed in cells suspended inside collagen gels. The results presented here demonstrate that integrin α1β1 acts as a feedback regulator of collagen synthesis both in vitro and in vivo. Firstly, α1 null animals show a higher rate of collagen synthesis in the dermis in vivo. Secondly, fibroblasts derived from α1 null cutaneous wounds show a reduced sensitivity to collagen gel induced downregulation of collagen mRNA synthesis, as compared to their wild-type counterparts. An increase in collagenase synthesis is also seen in the α1 null dermis and in collagen gel suspended fibroblasts. While dermal thickness is normal in the α¹ null animals, an increase is seen in skin thickness of α¹ null but not α¹ heterozygote animals on a background of collagenase resistant collagen. Increased expression of both collagen and collagenase mRNA are seen in experimental granulation tissue in α¹ null animals, but their ultimate accumulation of collagen is normal, probably due to non α¹ dependent paracrine regulators of collagen turnover.