Memory that food is inedible in Aplysia arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that NO functions during training as a signal of attempts to swallow. However, it has been shown that NO may also be released in other contexts affecting feeding, raising the possibility that its role in learning is unrelated to signaling attempts to swallow. We confirmed that NO during learning signals attempts to swallow, by showing that a variety of behavioral effects on feeding of blocking or adding NO do not affect learning and memory that a food is inedible. In addition, histamine had effects similar to NO on learning that food is inedible, as expected if the transmitters are released together when animals attempt to swallow. Blocking histamine during training blocked long-term memory, and exogenous histamine substituted for attempts to swallow. NO also substituted for histamine during training. Histamine at concentrations relevant to learning activates neuron metacerebral cell (MCC). However, MCC activity is not a good monitor of attempts to swallow during training, since the neuron responds equally well to other stimuli. These findings support and extend the hypothesis that NO and histamine signal efforts to swallow during learning, acting on targets other than the MCC that specifically respond to attempts to swallow.