Individuals weigh information about both rewarding and aversive stimuli to make adaptive decisions. Most studies of the orbitofrontal cortex (OFC), an area where appetitive and aversive neural subsystems might interact, have focused only on reward. Using a classical conditioning task where novel stimuli are paired with a reward or an aversive air puff, we discovered that two groups of orbitofrontal neurons respond preferentially to conditioned stimuli associated with rewarding and aversive outcomes; however, information about appetitive and aversive stimuli converges on individual neurons from both populations. Therefore, neurons in the OFC might participate in appetitive and aversive networks that track the motivational significance of stimuli even when they vary in valence and sensory modality. Further, we show that these networks, which also extend to the amygdala, exhibit different rates of change during reversal learning. Thus, although both networks represent appetitive and aversive associations, their distinct temporal dynamics might indicate different roles in learning processes.