A flow-through experimental system was designed to simulate habitat conditions encountered by American lobsters (Homarus americanus) during an eutrophication-driven mass mortality in the Long Island Sound during 1999. Seawater for the system was chemically conditioned through gas exchange and the addition of inorganic salts, resulting in simultaneous control of multiple environmental variables including: temperature (±0.5°C), dissolved oxygen (±0.3 mg L−1), sulfide (±1 μM) and ammonium (±3 μM). The system consisted of eight gas-tight, 280-L tanks, each capable of accommodating 22 lobsters, supplied with 0.4 L min−1 animal−1 of conditioned seawater. Outflows were fitted with ozone and ultraviolet sterilization so that lobsters could be exposed to infectious pathogens in varying doses to study effects of habitat on disease resistance, without contaminating the environment. Shelters are supplied in excess and lobsters utilizing them may be monitored to observe behavioral and physiologic responses without opening the tanks. With minimal alterations this system design can be applied to species with diverse structural requirements and to a wide range of ecologic issues including growth, survival and disease resistance under simulated habitat conditions.