Muscarinic acetylcholine receptors were extracted from rat cerebral cortex, hippocampus and brainstem membranes with 1% digitonin. Solubilized receptors retained both multiple receptor affinities and their regional selectivity in agonist binding (in terms of their affinity for carbamylcholine, brainstem greater than cortex greater than hippocampus). The affinity for carbamylcholine was increased 2-8-fold by solubilization; this increase was largely accounted for by an increase in the proportion of receptors displaying high affinity binding. No differences were observed in the size of receptor-detergent complexes from cortex or brainstem in gel filtration chromatography using a variety of gels and solubilizing agents. These findings indicate that not all of the factors underlying receptor heterogeneity and conformational state are removed or disrupted by solubilization.