Catecholestrogens (CE), 2-hydroxyestradiol, 2-hydroxyestrone and primary estrogens, estradiol and estrone were tested in their ability to compete for the high affinity uptake of [3H]-GABA into crude synaptosomal fractions. Aliquots of the crude synaptosomal fraction obtained from normal rats were incubated for 10 min at 37 degrees C with [3H]-GABA in the presence, or absence, of estrogens and catecholestrogens. Neither estradiol nor estrone modified the specific [3H]-GABA uptake into crude synaptosomal fractions. On the contrary, CE significantly affected the specific [3H]-GABA uptake in a dose-dependent manner: low concentrations of CE enhanced the uptake; this effect disappeared with high concentrations of the compounds. The stimulatory effect of CE on [3H]-GABA uptake was blocked when samples were coincubated with nipecotic acid, thus suggesting that this effect is specific rather than the result of non-specific interactions of CE with the hypothalamic membrane.