Treatment of the skin with the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate leads to a reduction of the collagen content of the dermis of the mouse. The collagen degradation as well as synthesis is affected by the tumor promoter, the effect on degradation being more pronounced at the beginning of the treatment. The collagenolytic activity that can be extracted from the dermis is increased 5- to 6-fold during the first five applications and approximately 2-fold at later times. The uptake of [14C]proline in both total protein and NaCl-soluble collagen is doubled, but the increase of collagen synthesis does not restore a normal collagen content in the dermis, as it is accompanied by an elevated level of collagenolytic activity.