OBJECTIVE To evaluate the potential interaction/contribution of inductive and deleterious effects of tobacco compounds on human osteoblastic cells cultured on plasma-sprayed titanium implants exposed to combinations of nicotine, acrolein, and acetaldehyde. Cell response was assessed as proliferation and function. METHODS Titanium implants, seeded with human bone marrow-derived cells (first subculture), were cultured in osteogenic-inducing conditions for 28 days in the absence (control) and in the presence of tobacco compounds to assess (1) the dose-dependent profile of acrolein (0.01 to 0.12 mmol/L) and acetaldehyde (0.1 to 6 mmol/L) and (2) the effect of the simultaneous exposure to combinations of nicotine, acrolein, and acetaldehyde. In later experiments, seeded implants were exposed to two different concentrations of nicotine (1.2 mmol/L, known to have inductive effects on cell behavior, and 2.4 mmol/L, reported to elicit deleterious effects on cell behavior) with acrolein, acetaldehyde, or both, at a concentration that inhibits 50% (IC50). RESULTS Acrolein and acetaldehyde caused dose-dependent inhibitory effects at levels similar to and greater than 0.03 and 0.1 mmol/L, respectively; IC50 regarding cell viability/proliferation and alkaline phosphatase was 0.06 mmol/L for acrolein and 0.3 mmol/L for acetaldehyde. Matrix mineralization was prevented at levels higher than 0.03 mmol/L acrolein and 0.1 mmol/L acetaldehyde. Exposure to a combination of nicotine 1.2 mmol/L with acrolein (0.06 mmol/L), acetaldehyde (0.3 mmol/L), or both resulted in a cell behavior intermediate to that observed in nicotine-treated cultures (induced cell response) and aldehyde-treated cultures (deleterious cell response). On the other hand, exposure to nicotine 2.4 mmol/L with acrolein (0.06 mmol/L), acetaldehyde (0.3 mmol/L), or both caused cumulative cytotoxic responses. CONCLUSIONS Results suggest that interactions of tobacco compounds on osteoblasts might contribute to the overall effects of tobacco use on implant osseointegration and long-time survival.