The mechanical strength development of healing wounds depends on the formation of collagen fibrils bridging the wound cleft. A considerable deposition, degradation, and remodeling of these fibrils takes place influencing the mechanical strength of the healing wounds. A method for studies of wound collagen metabolism in vivo is delineated, enabling determination of collagen deposition per hour in rat colon anastomoses and skin incisional wounds. Labeled proline was incorporated into wound collagen with a flooding dose of unlabeled proline, reducing errors introduced by proline recycling and proline de novo synthesis. The mechanical strength was determined by a materials testing machine. In both colon anastomoses and skin wounds a substantial increase in collagen deposition was observed at Day 2, reached a maximum at Day 6, and was still relatively high at Day 12 during the remodeling of collagen fibers in the wound cleft. The collagen deposition in colon anastomoses at Day 6, however, was 10-fold higher compared with that of the skin incisional wounds. The time course of the collagen deposition was much alike in colon anastomoses and skin incisional wounds reaching a maximum at Day 6. The mechanical strength of these two rather different types of wounds was increased correspondingly and to the same level during the 1st week of healing. The measurements of collagen deposition, collagen content, and biomechanical strength indicated a substantial turnover of newly synthesized and deposited collagen during the early phases of wound healing. On the basis of this, it seems obvious that even small disturbances to the balance between collagen synthesis, deposition, collagen cross-linking, and collagen degradation/remodeling may result in defective wound healing.