Semi-synthetic tetracyclines are commonly used antibiotics that also seem to play an important role in the modulation of the immuno-inflammatory imbalance, verified in several bone diseases. The association of a therapeutic agent (that prevents bacterial infection and induces tissue formation) to a biomaterial aiming to repair/regenerate bone defects could contribute to a more predictable clinical outcome. The present study intends to evaluate the proliferation and functional activity of osteoblast-induced human bone marrow cells, cultured on the surface of hydroxyapatite (HA) and Bonelike, in the presence of therapeutic concentrations of doxycycline and minocycline. First passage bone marrow cells were cultured for 35 days on the surface of HA and Bonelike discs, in the absence or presence of 1 microg ml(-1) doxycycline and minocycline. Cultures performed in standard tissue culture plates were used as control. Doxycycline or minocycline induced cell proliferation and increased the extent of matrix mineralization in osteoblastic cell cultures established in the three substrates. Also, an improved biological behavior was verified in seeded Bonelike compared with HA. The results suggest that the local delivery of tetracyclines might associate the antimicrobial activity in implant-related bone infection with an eventual induction of osteoblastic proliferation and maintenance of the characteristic biological activity of these cells.