Since the first description of lysosomes, most studies with these cytoplasmic organelles have been conducted in sucrose solutions containing little or no inorganic ions. Lysosomal enzymes have been characterized by their structure-linked latency in sucrose solutions of very low ionic strength. The data in this report illustrate that isotonic concentrations of certain inorganic ions can replace sucrose for the purpose of retarding osmotic lysis of liver lysosomes and thus preserving the latent properties of lysosomal enzymes. Acid phosphatase, β-glucuronidase, β-galactosidase and aryl sulfatase were the lysosomal marker enzymes measured. Iso-osmotic concentrations of potassium chloride and Hanks' Balanced Salt Solution were found to be suitable substitutes for sucrose in maintaining the structural integrity of lysosomes at neutral pH and 37°. Certain steroidal and non-steroidal anti-inflammatory drugs, such as hydrocortisone, chloroquine, acetylsalicylic acid, phenylbutazone, indomethacin and flufenamic acid, inhibited the release of several enzymes from lysosomes incubated in isotonic salt media. Further, the catecholamines, norepinephrine, epinephrine and isoproterenol, were found to inhibit lysosomal enzyme release in salt media. Similar lysosome membrane-stabilizing actions were obtained with cyclic 3',5'-adenosine monophosphate and its N 6, O 2′-dibutyryl analog. The data reveal that sucrose can be replaced by certain salt solutions for the purpose of maintaining the integrity of lysosomes or demonstrating drug-induced lysosome membrane stabilization in vitro.