In this paper, we simulate the effects of hippocampal lesions on Pavlovian conditioning with an existing neural network model. According to the model, the hippocampus sends a diffuse discrepancy signal that modulates efficacies of synapses from primary sensory to polysensory areas. We hypothesize that this signal lessens the detrimental effects of momentary nonreinforcement and weaker cues on such efficacies in Pavlovian conditioning. Hippocampal lesions are thus hypothesized to exacerbate both detrimental effects. To test this hypothesis against some relevant animal evidence, we ran two computer simulations using simple feedforward neural networks with two hidden layers, designed according to the model. Hippocampal lesions were simulated by removing the networks’ hippocampal units. Networks were trained in various conditions involving momentary nonreinforcement and reinforcement of differently salient cues. The results were reasonably consistent with animal evidence that hippocampal lesion is more disruptive of long-delay than short-trace conditioning (Simulation 1) and backward more than contiguous-trace conditioning (Simulation 2). Implications, limitations, and future directions are discussed.