Metal ions are often used to block calcium channels in various tissues, including synaptosomes. In the present study, Fura-2 was used to determine the effectiveness of various metal ions as calcium channel blockers in rat brain synaptosomes in vitro. In buffer solutions, La3+ and Cd2+ increased the Fura-2 fluorescence in a manner similar to Ca2+. Ni2+ and Mn2+ appeared to be fluorescence quenching cations, and Sr2+ and Co2+ had little effect on the fluorescence of Fura-2. In suspensions of synaptosomes under resting conditions, Cd2+, Ni2+ and Mn2+ were found to be not suitable for use in synaptosome studies. On the other hand, La3+ and Co2+ had little effect on the Fura-2 fluorescence of resting synaptosomes, and under depolarizing conditions, La3+ and Co2+ decreased the Fura-2 fluorescence. These results, therefore, suggest that La3+ and Co2+ may be suitable as calcium channel blockers in synaptosome studies.