Four commercial nonionic polyoxyethylene detergents were compared with Triton X-100 in terms of physicochemical properties and interaction with an integral membrane protein, phosphatidylinositol kinase. Tergitol 15-S-9, Tergitol TMN-10, polyoxyethylene 10 lauryl ether, and polyoxyethylene 10 tridecyl ether possess aliphatic hydrophobic moieties and therefore do not absorb significantly in the ultraviolet region. Like Triton X-100, these detergents have cloud points well above the physiological temperature range and partial specific volumes greater than 0.9 cm3/g. Critical micelle concentrations range from 0.02 to 0.03% with the exception of Tergitol TMN-10, for which the value is about 0.15%. All five detergents support activity of phosphatidylinositol kinase from rat liver in a mixed micellar assay and show similar ionic strength dependences for solubilization of the enzyme. Enzyme/detergent mixed micelles are somewhat smaller with Triton X-100 than for the other detergents. The data presented suggest that these detergents may be generally substituted for Triton X-100 in applications where uv invisibility is important.