Bipolar disorder can be understood as a disorder of behavioral regulation. Manic and depressed individuals are impaired in the titration of appetitive arousal, possibly at the level of neuronal plasticity. An experiment in which fixed 5% CO2 stimulates respiration and blocks satiety tests the regulation of appetitive arousal. In preliminary analysis of data from 35 individuals (24 with bipolar disorder) individuals with bipolar disorder were more likely to fail to find a stable state of respiratory adjustment to CO2. If confirmed, the unstable respiratory response to CO2 may prove useful as a bipolar-disorder endophenotype.