The effect of adenosine on 45Ca2+ uptake by rat brain synaptosomes stimulated by electrical pulses was investigated. 45Ca2+ uptake was voltage dependent. Adenosine (1 nM-1 microM) decreased the uptake of 45Ca2+ induced by electrical stimulation (amplitude, 20 V; duration, 400 microseconds; frequency, 10 pulses/s) in a concentration-dependent manner. At a concentration of 1 microM, adenosine almost abolished the 45Ca2+ uptake induced by electrical stimulation (92.9 +/- 5.3% inhibition), but when the calcium uptake was induced by high-K+ (60 mM) medium, the effect of adenosine (1 microM) was smaller (43.8 +/- 5.2% inhibition). The inhibitory effect of 1 microM adenosine on calcium uptake induced by electrical stimulation was antagonized by 1,3-dipropyl-8-p-sulfophenylxanthine (5 microM). The possibility that adenosine interacts with the calcium channels opened by electrical stimulation is discussed.