The authors describe an 18-compartment hybrid computer multiple model of the uptake and distribution of halothane. This model uses 88 equations and 124 parameter settings. Three submodels are incorporated into the basic model: 1) The mass transport of halothane is simulated on the digital portion of the hybrid computer. 2) A breath-by-breath pulmonary model with two compartments describes air pressure-flow relations in the airway system. 3) A beat-to-beat cardiovascular model with 15 compartments describes in detail blood pressure-flow relations. In addition, a baroreceptor-heart rate loop is included: an increase in arterial pressure causes a decrease in heart rate. The slope of the baroreceptor response is progressively decreased by halothane until at 2 per cent there is no response.The model of halothane uptake and distribution is separate from the blood and air pressure-flow models, but is, in effect, driven by them. Myocardial “contractility” (stroke volume) and certain regional vascular resistances can be affected by the concentration of halothane in one or any proportion of any combination of three compartments: arterial blood (arteriolar concentration), cerebral gray matter, or myocardial. In turn, these factors significantly affect the uptake and distribution of halothane.The responses to three steady-state concentrations, as well as to a step change in concentration from 0 to 2 per cent, were examined. Twenty-four outputs were recorded, including halothane concentrations in ten compartments; myocardial “contractility”; left and right ventricular and right atrial pressures; cardiac output; stroke volume, R–R interval; and blood flows in six regions. Two variables—alveolar concentration of halothane and arterial blood pressure—were recorded during a step change of 0 to 5 per cent.The model describes the appropriate steady-state and dynamic cardiovascular responses to halothane. It also demonstrates the complex interrelationships among cardiac output, regional blood flow distribution, and the uptake and distribution of halothane. During step changes in halothane concentration, most of the responses occur early, a phenomenon also seen in man and goats.Thus, the model is useful not only for representing organ and tissue halothane concentrations, but also for gaining new insights into cardiovascular alterations produced by rapidly changing concentrations of halothane and into the complex interactions between the circulation and the uptake and distribution of halothane.