Catecholamine release from rat pheochromocytoma (PC12) cells has been observed at zeptomole levels using dc-amperometric detection with carbon fiber microelectrodes. Time-resolved individual exocytic events from PC12 cells have been recorded and analyzed with 1.2 ms time resolution. The average area under 1912 current transients from 13 PC12 cells corresponds to 190 zmol (114,300 molecules per release event). The average width at half-height of these current transients is 9.3 ms, in agreement with the time frame of exocytosis. The detection limit of the method reported here is as low as 31 zmol. This is the first report of direct electrochemical observation of quantal release from PC12 cells. The successful application of this electrochemical scheme to monitor catecholamines released from small vesicles also suggests that it may be possible to apply this technique to monitor quantal release from synaptic vesicles.