The authors have described a basic hybrid computer multiple model of the circulation, ventilation, and uptake and distribution of halothane in a companion paper. A multiple model consists of two or more submodels, each of which is complete in itself and could operate independently. In a multiple model, however, each submodel interacts with the others. The present paper describes the addition of a CO2-control loop (submodel), through which the partial pressure of CO2modulates ventilation, as well as myocardial “contractility,” arterial pressure, cardiac output, and regional vascular resistances. The concentration of halothane modifies these CO2-induced modulations. The CO2- and halothane-induced changes in ventilation and circulation in turn modify the uptake and distribution of halothane. Thus, a complex set of interrelationships among the submodels and compartments exists.