Abstract Platelet-derived growth factor (PDGF) and the glucocorticoid dexamethasone combined with a collagen carrier matrix (CM) induced regeneration of the periodontium in monkeys. Regeneration was stringently defined as (1) new cementum, (2 new supra-crestal bone extending coronally from the residual alveolar interdental septum and (3) functionally-oriented periodontal ligament fibers attaching new cementum to new bone. A single application of PDGF/dexamethasone/CM or CM was placed in debrided lesions of experimental periodontitis displaying 3–5 mm of attachment loss associated with horizontal and angular bony defects. Regeneration, judged histologically by these criteria and quantified by computer assisted histomorphometry after 4 weeks, was present only in PDGF/dexamethasone/CM treated lesions and not in those treated with CM or debridement alone. PDGF/dexamethasone/CM induced 5-fold more new cementum and ligament, and 7-fold more supra-crestal bone than control treatments. The presence of substantial amounts of regenerated periodontium including increased height of the alveolar bone: fill of vertically resorbed interdental alveolar septa in PDGF/dexamelhasone/CM treated lesions suggests that this combination may provide a new therapeutic agent for the regeneration of lesions of pertodontitis associated with horizontal as well as angular bony defects.