Purpose: Reconstructive surgical treatment with osteopromotive membranes has become an integral part of implant dentistry. Nevertheless, there are still instances in which this technique alone is of limited or no benefit. The aim of the present study was to determine whether a combination of titanium membranes coated with transforming growth factor ß1 (TGF-ß1) and insulin-like growth factor I (IGF-I) is of value in the regeneration of so-called critical-size defects in the rat model. An analysis was made of whether or not locally administered antibiotics are deleterious to bone regeneration. Materials and Methods: A total of 24 rats were included in the study and were divided into 4 groups, each with 6 animals. Critical-size defects were created bilaterally and covered by titanium membranes coated with (1) polylactide, (2) polylactide and clindamycin, (3) polylactide and growth factors, or (4) polylactide, clindamycin, and growth factors. All 24 contralateral defects were covered by titanium membranes without any substrate (controls). Four weeks after treatment the animals were sacrificed. Results: In groups 3 and 4, most defects showed thin but almost complete bridging of the defects with new bone formation. In particular, clindamycin had no inhibitory effect on the regeneration of bone. Nevertheless, after 28 days, there was no significant difference between the individual groups (including controls) with respect to the total amount of newly formed bone. Discussion and Conclusion: These results support the hypothesis that coating titanium membranes with TGF-ß1/IGF-I leads to almost complete bony bridging of critical-size defects without voluminous carrier materials. Moreover, simultaneous administration of clindamycin seems possible.