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The zwitterionic detergent, 3‐[(3‐cholamidopropyl)‐dimethylammonio]‐1‐propanesulfonate (CHAPS), is mild, non‐denaturing, and extensively used for solubilizing membrane proteins and receptors. We report here that the critical micelle concentration (CMC) of CHAPS is dependent on the concentration of NaCl in the solution. Thus, the CMC of CHAPS decreases from 6.41 mM in absence of any salt to 4.10 mM in presence of 1.5 M NaCl. The logarithm of the CMC values appear to have a linear relationship with the salt concentration. Such changes in CMC with ionic strength have important implications in solubilization of membrane‐bound neuronal receptors. This is shown by optimal solubilization of the serotonin receptor type 1A (5‐HT_1A) from bovine brain hippocampal crude (native) membrane by CHAPS at premicellar concentration under high salt conditions.