For long-duration space missions, a Controlled Ecological Life Support System (CELSS) is the most economical means of producing the food required by the crew. From a systems design perspective, it would be advantageous to be able to grow all the plants hydroponically, in one large system sharing the same nutrient solution (polyculture). However, very little research has been performed to determine how crop plants interact with one another when grown together hydroponically, although evidence for soil-based interaction between plants does exist. In this study, lettuce and tomato plants were grown in a shared, recirculating nutrient solution to examine the effects of mutual interaction. Only nutrient solution effects were investigated, no atmospheric interactions were examined. Growth of the first crop of lettuce was unaffected or even slightly enhanced by growing it in polyculture with tomato plants. All subsequent lettuce plants were significantly smaller than those grown in monoculture, however, averaging up to 60% lower in dry weight. The results of these experiments demonstrate that there are significant plant-plant interactions in hydroponic nutrient solutions. Possible explanations for this kind of interaction are described and analyzed with respect to their influence on CELSS design.