Associative learning is a fundamental form of behavioral plasticity. It is indispensable for many organisms to appropriately respond to external cues predicting danger or reward for survival. The major monoamine octopamine plays a vital role in various types of learning and memory processes. Previous studies have shown that dopamine and octopamine are key mediators of olfactory learning. While dopamine regulates both aversive and appetitive learning, octopamine is known to mediate appetitive but not aversive learning. In order to clarify whether octopamine is also important for aversive learning, we employed negatively reinforced olfactory Pavlovian conditioning. Wild-type Canton-S flies showed robust learning and normal short-term memory. However, the flies deficient in the octopamine receptor Octβ1R exhibited poor learning but normal short-term memory. This suggests that the octopamine’s signal through the Octβ1R receptor is critical for aversive learning. Studies are in progress to identify the key neural site where Ocβ1R regulates aversive learning.