The effect of activated factor XIII (FXIIIa), the transglutaminase of blood coagulation, on some cellular functions was studied in skin and lung fibroblasts in vitro. FXIIIa repressed the overall protein synthesis and mainly collagen synthesis in a concentration-dependent manner and induced modifications in the proportion of the different types of newly synthesized collagen. The repression of collagen synthesis occurred in cells cultured on plastic (-40%), on coated fibronectin (-53%), on coated collagens (-38%) and within a collagen lattice (-16%). Preincubation of the cells with FXIIIa and labelling in its absence also resulted in such an inhibition. However, when embedded into a fibrin lattice cross-linked by FXIIIa, fibroblasts displayed a higher biosynthetic activity than in untreated fibrin gel. These results suggest that FXIIIa acts through a modulation of the cell-matrix interactions.