The effects of chronic administration of growth hormone-releasing factor (GRF) on wound healing were studied in rats. Cutaneous wound strength was measured by tensometry at 5, 10, and 14 days postwounding in rats implanted with a slow-release pellet which contained a compressed mixture of a fatty acid and [desamino Tyr 1, d-Ala 2, Ala 15]hGRF(1–29)NH 2 or the fatty acid alone. There was a significant increase in wound tensile strength in GRF-treated rats compared to controls at each measurement: Day 5, 130 ± 12 vs 97 ± 14 g; Day 10, 402 ± 18 vs 280 ± 11 g; Day 14, 830 ± 17 vs 614 ± 14 g ( P < 0.01 for each value). Granulation tissue obtained from subcutaneously implanted polyvinyl alcohol sponges encased in silicone tubing was also studied. The amount of collagen deposited in the granulation tissue was estimated by measuring the hydroxyproline (Hyp) content of sponges retrieved 5, 10, and 14 days postinsertion from GRF-treated and control rats. Hyp content (nmole/mg sponge) was similar in both treated and control animals at each measurement: Day 5, 1.7 ± 0.2 vs 2.2 ± 0.2; Day 10, 31.9 ± 4.1 vs 26.7 + 0.4; and Day 14, 41.6 ± 7.3 vs 38.5 ± 4.4. Hyp/proline, Hyp/glycine, and glycine/total amino acid ratios, evaluated after 10 days, were also similar in both groups. Collagen from the granulation tissue of sponges retrieved after 14 days from treated and control rats was studied by electron microscopy (magnifications, 7,100 and 22,720). The intercellular spaces in the sponges of the control rats were sparsely covered by collagen fibrils, in contrast to the intercellular spaces in the sponges of the treated rats, which were completely filled with collagen fibrils. These results demonstrate that chronic administration of GRF for 14 days increases wound strength during the early stage of healing in rats. In addition, GRF does not stimulate collagen deposition in granulation tissue, but accelerates collagen maturation instead. We postulate, therefore, that this effect is responsible for the enhanced cutaneous wound strength seen at 10 and 14 days postwounding in GRF-treated rats.