An in vivo conditioning procedure consisting of light paired with the direct application of 5-HT to the exposed but otherwise intact nervous system of Hermissenda produces a long-term modification of phototactic behavior. The long-term change in phototactic behavior produced by in vivo conditioning is dependent upon pairing light with 5-HT. In this paper, we investigate neural correlates of in vivo conditioning detected in 2 different identified photoreceptors. We found that in vivo conditioning produces a short-term and long-term enhancement of light-evoked generator potentials recorded from medial and lateral B- photoreceptors. We show that short-term enhancement is not dependent upon pairing light with 5-HT, is observed in both lateral and medial B- photoreceptors, and is expressed by a larger peak and plateau phase of light-evoked generator potentials. In contrast to short-term enhancement, we found that long-term enhancement is dependent upon pairing light with 5-HT, is detected in only lateral B-photoreceptors, and is expressed by a larger steady-state plateau phase of light-evoked generator potentials. We also present evidence that the direct action of 5-HT interacting with light- and/or voltage-dependent processes is sufficient to mimic the effects of in vivo conditioning on long-term enhancement. These results suggest that long-term enhancement may contribute to modified phototactic behavior in Hermissenda produced by 1-trial in vivo conditioning.