Culturing human fibroblasts in a three‐dimensional collagen matrix leads to a reduction of collagen I by more than 90%, both on the level of mRNA steady‐state as well as protein. In order to differentiate changes in de novo transcription and posttranscriptional control, nuclear run on assays and pulse/chase experiments determining mRNA stability were used. Our results indicate that de novo transcription of the COL1A1 gene and proα1(I)collagen mRNA half‐life are both decreased by 50% in fibroblasts grown in three‐dimensional collagen lattices as compared to monolayer cultures. The extracellular matrix therefore elicits signals which are transduced from the cell surface to the inside of fibroblasts resulting in a specific reprogramming of transcriptional as well as posttranscriptional processes.