We use molecular dynamics simulations to investigate the effects of halothane, a volatile anesthetic, and hexafluoroethane (HFE), its nonimmobilizer analogue, on the physical properties of a fully hydrated polyunsaturated (1-stearoyl- 2-docosahexaenoyl-sn-glycero-3-phosphocholine) lipid bilayer in the liquid crystalline fluid lamellar phase, L-alpha. In addition, we discuss the results obtained comparing them to previous studies on saturated lipid bilayers with the same solutes. At the analyzed concentration (25% mole fraction), the halothane molecules are located preferentially near the upper part of the lipid acyl chains, while the HFE molecules prefer the hydrocarbon chains and methyl trough region. In the case of halothane in the polyunsaturated lipid bilayer, there is an additional density maximum at the membrane center not observed in saturated lipids. The subtle effect of the solutes on the structural properties of the highly unsaturated lipid bilayer and the properties of the membrane interior is somewhat different from that observed for saturated lipids. Here, these differences are interpreted in terms of the unique properties of the polyunsaturated lipid bilayers. The effect of anesthetic molecules on the electrostatic properties of the membrane interface is similar for saturated and polyunsaturated lipid bilayers and is characterized by a change in the most probable orientation of the lipid headgroup dipoles, which point toward the membrane interior for halothane and are basically unchanged for HFE, i.e., point toward the water phase. The different distributions of anesthetic and nonimmobilizer molecules within the lipid bilayer systems seem to be a generic feature in simple models of biological membranes and are similar to those observed in systems with saturated lipids. Since polyunsaturated and other unsaturated lipids are ubiquitous in cell membranes, it is plausible to generalize these features to the more complex biological membranes.