The phenomenon of paired-pulse facilitation (PPF) was exploited to investigate the role of presynaptic mechanisms in the induction and maintenance of long-term synaptic plasticity in the neocortex. Long-term potentiation (LTP) and depression (LTD) were induced without afferent activation by applying tetani of intracellular pulses. Our results show that synaptic modifications closely resembling LTP and LTD can be induced by postsynaptic activation alone. The polarity of these synaptic modifications depends on initial properties of the input, as indicated by a correlation between initial PPF ratio and post-tetanic amplitude changes: inputs exhibiting strong PPF, which might be associated with low release probability tend to be potentiated, while inputs with small PPF are more likely to show depression. Maintenance of both LTP and LTD involve presynaptic mechanisms, as indicated by changes in PPF ratios and in failure rate after LTP or LTD induction. Presynaptic mechanisms could include changes in release probability and/or in the number of active release sites. Because induction was postsynaptic, this supports the notion of a retrograde signal. The relative contribution of pre- and postsynaptic mechanisms in the maintenance of long-term synaptic modifications depends on the initial state of the synaptic input and on LTP magnitude. PPF changes were especially pronounced in inputs which had initially high PPF and underwent strong potentiation. Since LTP and LTD are associated with changes of PPF ratios these synaptic modifications do not only alter the gain but also the temporal properties of synaptic transmission. Because of the LTP associated reduction of PPF, potentiated inputs profit less from temporal summation, favouring transmission of synchronized, low frequency activity.