Ontogenetic development and Ca2+-dependence of the K+-stimulated release of [3H].gamma.-aminobutyric acid (GABA) were studied by two different methods using tissue slices in vitro. The results indicate that, in the developing rat cortex, the K+-stimulated release of [3H]GABA is initially very low but it develops rapidly during the second and third postnatal weeks. This supports an earlier study which concluded that, during the cortical ontogeny, the ratio of stimulated:resting release of [3H]GABA increased at the fastest rate about 9-12 days after the birth, thus preceding the formation of GABAergic synapses by about 10 days. Furthermore, most of the early postnatal release observed in the presence experiments is Ca2+-independent. An important Ca2+-dependent component of the release appears at later developmental stages and it also seems to develop faster than the GABAergic synapses. The present study suggests that the stimulus-coupled release of GABA in the rat cortex profoundly changes during the ontogeny, both quantitatively (the period of rapid development) and qualitatively (with respect to Ca2+-dependence). These observations, possibly reflecting changes in the association of GABA release with different structures (e.g. initially axonal growth cones, then neuronal dendrites and only at later stages GABAergic synapses) may be important in the evaluation of the putative role of GABA in synaptogenesis.