Synaptic plasma membranes from the brain are known to have specific binding sites for several steroid hormones, but the mechanism of membrane trans-duction of steroid signals is not understood. In this study, corticosterone was found to stimulate 45Ca2+ uptake in brain synaptosomes upon depolarization of the synaptosomes by high K+ (70 mM). The stimulation of the depolarization-dependent 45Ca2+ uptake by corticosterone is concentration dependent, with the maximal effect occurring at steroid concentration of 5 – 10 × 10–7M (70–80% above control). The EC50 is estimated as 1.3 × 10–7M, which is almost identical to the Kdof the specific binding of the steroid to synaptic membranes (1.2 × 10–7M) reported previously. The stimulation of 45Ca2+ uptake in brain synaptosomes is specific to corticosterone and other glucocorticoids (cortisol, dexamethasone and triamcinolone); gonadal steroids (17β-estradiol, progesterone and testosterone) are ineffective. [3H]Nitrendipine binding was used to examine the effect of corticosterone on voltage-dependent Ca2+ channels. No effect on [3H]nitrendipine binding was found when disrupted synaptic membranes were preincubated with the steroid. However, a significant increase of membrane binding of [3H]nitrendipine was found when intact synaptosomes were first preincubated with the steroid at 37°C and then disrupted. Steroid preincubation of synaptosomes at 0°C was ineffective. Since preincubation at 37°C is required, it appears that metabolic processes modulating Ca2+ channel activity are involved in th