Calcium is required for antigen presentation. In the past study, we found that cocaine increased macrophage antigen-presenting activity. To investigate whether cocaine induces a calcium influx into macrophage cytosol, we used Fura2-AM to directly test the macrophage intracellular calcium concentration [Ca2+]i under the influence of different concentrations of cocaine after macrophages were primed by IFN-gamma or LPS. We report here that cocaine increases the IFN-gamma-primed macrophage [Ca2+]i, but it does not affect the LPS-primed macrophage [Ca2+]i. Furthermore, calcium blocker, nifedipine, blocks the effect of cocaine, suggesting that extracellular calcium enters the cytosol through the L-channel.