Rat brain membranes exhibiting stereospecific opiate binding activity were solubilized by sonication and detergent treatment. The active material could be bound to an affinity column containing 6-succinylmorphine but could not be eluted with free agonist. Although two protein peaks could be eluted with NaCl, neither possessed binding activity; however, one to the peaks (A), in combination with an acidic lipid fraction, eluted subsequently from the column, showed stereospecific binding. Opiate ligands of the μ type bound to this protein/lipid mixture with an order of affinities closely correlating with those of the original membrane but one of two orders of magnitude lower; binding of δ, κ, and σ prototype opioids was considerably less. The protein/lipid mixture also competed with the membranes for μ ligands. These results suggest that the isolated protein-lipid complex may be a component of the opiate receptor and, specifically, the μ receptor or binding site. However, because of the lower affinities of μ opiates for this complex, it is conceivable that some essential membrane component is still missing. Preliminary analysis of peak A indicates that it contains a broad spectrum of protein bands, but it remains to be seen which of these are essential for activity.