At the neuromuscular junction, spontaneous miniature excitatory synaptic currents mediated by acetylcholine are considered elementary, "quantal" transmissions. These miniature conductances can be quantitatively dichotomized into a large-mode class whose mode is the mean of a normal, bell-shaped distribution and a small-mode class whose distribution is skewed to lower values with its mode being a fraction of the large-mode class. The large-mode class constitutes the population of synaptic signals originally utilized to formulate tenets of "quantal" transmission, which have been tacitly adopted in more recent studies of fast transmission at central synapses. Large-and small-mode conductance classes of inhibitory synaptic elementary conductances mediated by GABA have now been recorded in cultured hippocampal neurons (Vautrin J, Schaffner AE, Barker JL, 1991, Neurosci Lett 138:67). Pairs of hippocampal neurons were patchrecorded at optimal signal-to-noise and, using time course analysis, two elementary fluctuations (0.1-0.3 nS and 1-2 nS) were found within synaptic conductances evoked either by presynaptic action potentials or by presynaptic terminal stimulation. These results were interpreted with a simple model that shows how different frequencies of unitary GABA release can generate either small-mode, skew-distributed conductance (0.5-3 kHz) or large-mode, normally-distributed conductances (210 kHz). Only the latter satisfies the original tenets of the classic quantal theory.