Background: Immunosuppressive agents have been recognized as a factor affecting bone metabolism. We investigated the consequences of the administration and withdrawal of cyclosporin A/nifedipine on bone around titanium implants to observe whether these changes occur and if they are reversible. Methods: Twenty-eight New Zealand rabbits were included in the study. Following anesthesia, the tibiae surface was exposed, and 2 screw-shaped implants 7.0 mm in length and 3.75 mm in diameter were placed bilaterally. The animals were randomly assigned to 1 of 4 experimental groups and received daily subcutaneous injections for 14 days: groups A and C were injected with vehicle while groups B and D received cyclosporin A (10 mg/kg) plus nifedipine (0.5 mg/kg). Groups A and B were sacrificed 14 days and groups C and D 42 days postoperatively. The degree of bone contact with the implant surface and the bone area within the limits of the threads of the implant were measured. Results: Intergroup analysis revealed no significant difference (P >0.05) in the degree of bone contact with the implant surface between the control and test groups on days 14 and 42. In contrast, the treated animals demonstrated a significant (P <0.05) decrease in the bone area within the limits of the threads of the implant in both periods. Conclusions: The data of the present study suggest that the use of cyclosporin A/nifedipine may influence bone healing around titanium implants. This observation may have important clinical implications.721013911397