This study investigated the biological response of fibroblasts cultured from uninjured skin and granulation tissue from different stages of healing wounds to the three isoforms of platelet‐derived growth factor. Fibroblasts were derived by explant culture from the skin or the granulation tissue that formed within open mesh nylon Schilling‐Hunt chambers (postoperative days 10, 20, 30, and 50) which had been implanted subcutaneously in the backs of domestic pigs. Cells were cultured under identical conditions in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. Mitogenic activity was measured with 3H‐thymidine incorporation into DNA. Fibroblasts from normal skin responded equally well to all of the platelet‐derived growth factor isoforms in the mitogenic assays. All of the wound fibroblasts exhibited a decreased response to platelet‐derived growth factor compared with those from skin. Granulation tissue fibroblasts responded to platelet‐derived growth factor BB, less to platelet‐derived growth factor AB, and poorly to platelet‐derived growth factor AA. These results correlated with a significantly decreased growth rate of fibroblasts in culture from both 30‐ and 50‐day postsurgical wound tissue compared with normal skin. Western blot studies of cell membrane extracts showed that wound fibroblasts contained less than 20% as many platelet‐derived growth factor‐α receptors as found in fibroblasts cultured from normal skin. No significant difference in the amount of platelet‐derived growth factor‐β receptor was detected. The decreases in platelet‐derived growth factor‐α receptors are sufficient to account for the diminished response of the wound fibroblasts to all platelet‐derived growth factor isoforms and the differential loss of responsiveness to platelet‐derived growth factor AA. These results show that fibroblasts derived from granulation tissue of pig skin wounds exhibit a decreased growth response to platelet‐derived growth factor and a decreased growth rate in culture media as compared with fibroblasts derived from uninjured skin. How these differences may relate to the physiologic characteristics of normal and healing‐impaired wounds is considered.