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An explicit adaptive controller for the control of closed-circuit anesthesia (CCA) has been developed. This system controls the end-tidal oxygen and anesthetic gas concentrations as well as the circuit volume. The CCA process was modeled by writing mass balance equations. Simplifying assumptions yielded a bilinear single-input-single-output model for the anesthetic gas concentration and a bilinear multiple-input-multiple-output model for the circuit volume and oxygen concentration. One-step-ahead controllers were used to control these two subsystems. Simulations showed that the control performance was most sensitive to the gas uptakes. Three independent, least-mean-squares estimation schemes were implemented to estimate the uptakes of oxygen, nitrous oxide, and anesthetic gas. These estimates were used in the control law and resulted in explicit adaptive control. The performance of the adaptive controller was compared to that of a fixed controller (with precalculated gas uptakes) in five animal experiments. The adaptive controller performed better than the fixed controller in all cases.