Two crops of lettuce (Lactuca sativa cv. Waldmann's Green) were grown in the Regenerative Life Support Systems (RLSS) Test Bed at NASA's Johnson Space Center. The RLSS Test Bed is an atmospherically closed, controlled environment facility for the evaluation of regenerative life support systems using higher plants. The chamber encloses 10.6 m2 of growth area under cool-white fluorescent lamps. Lettuce was double seeded in 480 pots, each containing about 250 cm3 of calcined-clay substrate. Each pot was irrigated with half-strength Hoagland's nutrient solution at an average total applied amount of 2.5 and 1.8 liters pot-1, respectively, over each of the two 30-day crop tests. Average environmental and cultural conditions during both tests were 23°C air temperature, 72% relative humidity, 1000 ppm carbon dioxide (CO2), 16h light/8h dark photoperiod, and 356 μmol m-2s-1 photosynthetic photon flux. After 30 days from seeding, average yield (g pot-1) for the first and second crop tests were 72 and 49 edible (shoot) fresh mass, 3.65 and 2.56 edible dry mass, and 0.44 and 0.45 inedible (root) dry mass, respectively. Averaging over both crop tests, the test bed met the requirements of 2.1 person-days of oxygen production, 2.4 person days of CO2 removal and 129 person days of potential potable water production. The satisfactory growth of both crops demonstrates the potential of lettuce for air revitalization and water production in a controlled ecological life support system. Differences in crop performance resulting from engineering system effects provides evidence of the resilience of biological systems.