Inhibition of nitric oxide synthase prior to conditioning has been previously found to reduce levels of hippocampal long-term potentiation. In the present experiments in the rat, the reduction of long-term potentiation by nitric oxide synthase inhibitors was highly conditioning-dependent. We have characterized the relative importance of the number of conditioning stimulus trains, pulse number, intensity, and pattern in the reduction of long-term potentiation by nitric oxide synthase inhibitors. Long-term potentiation was reduced relative to control values only when multiple conditioning stimulus trains were presented at maximal stimulus intensity; potentiation produced by an equivalent number and intensity of stimuli presented in a single conditioning train was not reduced by nitric oxide synthase inhibitors, and multiple-train-induced potentiation was sensitive to nitric oxide synthase inhibitors only when maximal stimulation intensity was employed. Another form of synaptic potentiation, primed-burst potentiation, was reduced by nitric oxide synthase inhibition, while homosynaptic and heterosynaptic depression were unaffected. Our results support the hypothesis that conditioning-dependent release of nitric oxide can contribute to long-term potentiation, but also show that its blockade by nitric oxide synthase inhibitors is dependent on the nature of the conditioning stimulus, and that long-term potentiation can be generated that is apparently resistant to the effects of these drugs.