Among many other abiotic variations in an estuarine ecosystem, osmotic stress is an inescapable part of life. Organisms living in such environments must cope with changing osmotic conditions by either behavioral or physiological adaptations. Pollutants may increase the physiological stresses that an osmoregulating animal may encounter. We have developed a flow-through system that exposes test species to insecticides and continuously changing salinity conditions. This system has provided an insight into how susceptibility of a species to an insecticide can be affected by changing concentrations of salinity. Toxicity tests using this system were conducted with two arthropod species that are found in saline habitats: mosquito Aedes taeniorhynchus (Wiedemann) and brine shrimp (Artemia sp.). Four insecticides—aldicarb, dimethoate, imidacloprid, and tebufenozide—were studied. Both species were exposed for 48 h to a concentration of various insecticides that would cause 50% of the population to die in hyperosmotic artificial sea water (ASW). The mortality rate for both species was more acute in increasing salinity (10–200% ASW) than in decreasing salinity (200–10% ASW) conditions. A. taeniorhynchus was more susceptible than Artemia when exposed to its hyperosmotic LC₅₀ concentration of toxicant while experiencing a change in salinity, e.g., adjusting to a changing salinity decreased the LT₅₀. Our results indicated a change in salinity; more importantly, the direction of change altered the susceptibility of these organisms.