In an effort to examine the effects of calcium blockers and adenosine on superoxide, hydrogen peroxide, and nitrite secretions by mouse peritoneal macrophages, we have utilized the phenol red method, the superoxide dismutase-inhibitable reduction of ferricytochrome c method, and the Griess reagent method to test products after treating periodate-elicited mouse peritoneal macrophages with verapamil, nifedipine, and adenosine. The results show that after treating the macrophages with chemicals 10 minutes before adding PMA (100 ng/ml), all three chemicals inhibited superoxide (O2-) and hydrogen peroxide (H2O2) secretions dose-dependently, yet they failed to suppress macrophage reactive oxygen intermediates (ROI) after a 24 hour treatment. On the other hand, calcium blockers, verapamil and nifedipine, could reduce nitrite secretion (NO2-), while adenosine did not show the ability to inhibit NO2-. This indicates that calcium, as a secondary messenger, is important for the production of ROI and RNI. The reason behind the loss of the ability to suppress macrophage ROI production in a 24 hour treatment remains unexplored.