We have recently demonstrated that genetic background significantly impacts on the blood pressure and heart rate response to hypoxia (Physiol. Genomics 20(1):15-20, 2005). Since hypoxia is considered a mediator of the acute and chronic cardiovascular complications of obstructive sleep apnea, we investigated whether genetic factors also influence the cardiovascular response to experimentally-induced obstructive apnea (OA) and simulated apnea (SA). In three strains of inbred mice (C57BL/6J, DBA/2J, and FVB/J) anesthetized with urethane (1.2g/kg), apnea was induced at end-expiration for 5s and 10s periods in spontaneously breathing (OA) and mechanically ventilated (SA; pancuronium, 0.2mg/kg bolus+0.003mg/kg/min) animals before and after administration of an autonomic ganglionic blocker (hexamethonium; 20mg/kg). In contrast to our previous findings with hypoxia, OA produced a marked hypertensive response in all three strains. However, strain impacted on the degree of bradycardia during OA, which was large in C57BL/6J and FVB/J mice, and effectively absent in DBA/2J mice. In C57BL/6J, but not FVB/J, mice the bradycardia was abolished with SA under mechanical ventilation. Cardiovascular responses to SA in all strains were eliminated by autonomic blockade. These data show that (1) DBA/2J mice, in contrast to the previous demonstration of marked bradycardia during hypoxia, unexpectedly do not produce bradycardia during apnea; (2) C57BL/6J mice exhibit a bradycardia that is dependent on input from thoracic afferents; (3) FVB/J mice exhibit a bradycardia despite the loss of thoracic afferent input, consistent with a potent pressure response eliciting a baroreceptor-mediated bradycardia. Thus, genetic background can affect both the pattern and magnitude of the cardiovascular response to apnea.