The effect of varying calcium and magnesium concentrations was observed on the development of long-term potentiation (LTP) in the CA1 region of the rat hippocampus maintained in vitro. Treatments which would be expected to lower the depolarization-induced influx of calcium into neuronal elements (i.e. lowering Ca²⁺ or raising Mg²⁺ in the perfusion medium) selectively antagonized LTP, while synaptic transmission, paired-pulse and frequency facilitation, as well as short-term (or post-tetamic) potentiation were all maintained. This suggests that LTP is unrelated to these short-term forms of plasticity, but is either a calcium-dependent process itself, or is dependent upon some other calcium-related phenomenon (such as transmitter release).