A study was undertaken to evaluate the antigenic potential of allogeneic freeze-dried skin (FDS) when used as a grafting material and to examine the clinical results when FDS is used for the correction of mucogingival problems in humans. FDS was obtained from an HLA-tissue-type donor according to Navy Tissue Bank protocol. Allogeneic FDS grafts were performed to correct mucogingival problems. In addition, periosteal fenestration was used in conjunction with approximately one-half of the grafts. Documentation with a standardized periodontal probe consisted of clinical measurements taken preoperatively and 8 weeks postoperatively. Blood samples were drawn prior to and at 1, 2, 3, 5, and 8 weeks postsurgically. Testing of blood samples for anti-HLA antibody was performed by use of a modified microcytotoxicity assay. Thirty-one patients received 36 FDS grafts involving 148 tooth sites. The FDS allografts resulted in a significant (P < 0.001) increase in the width of attached-type tissue (mean gain = 3.80 mm). Clinically, there was no sign of graft rejection, and serologically, all serum samples tested were nagative for the presence of anti-HLA antibody. FDS grafts used for the treatment of mucogingival problems in humans are nonimmunogenic as evaluated for anti-HLA antibody. The surgical procedure performed using FDS as a graft material resulted in a significant increase in the width of attached-type tissue.