When included in a free floating collagen lattice, several types of cells and fibroblasts attach to the collagen polymers, retract the gel, and their biosynthetic activity is repressed. Under similar conditions transformed pulmonary epithelial rat (PER) cells are unable to attach to the fibers and to significantly retract the lattice. Retraction can be induced by adding fibronectin (fn) and factor XIII (FXIII) together. This effect is fibronectin dose dependent and observed with a maximum efficiency for FXIII concentrations of 0.1 U/ml and above. Fibronectin or FXIII alone has only a limited effect on retraction. This experimental model allowed us to study the biosynthetic activity of PER cells under various degrees of cell interaction (control less than FXIII less than fn less than fn + FXIII) with their three-dimensional collagen support. The more the cells interacted with their support and retracted the gel, the more protein and collagen synthesis were reduced. This effect was observed for the products deposited in the cell layer and for those released in the medium. Increasing collagen concentration in a nonretracting lattice to a final density obtained in a maximally retracted lattice resulted in a much lower repression of biosynthetic activity. Fn and FXIII added at the same concentrations in monolayer cultures did not produce significant modification in biosynthetic activities. We propose that the regulation of the biosynthetic activity of adherent cells contracting the lattice is related to mechanical information resulting from the interactions between the cells and their support.