Dorsal penile nerve blocking (DPNB) has been used with success in decreasing neonatal stress during circumcision. This study was designed to confirm the effectiveness of lidocaine in DPNB and to demonstrate that chloroprocaine, a shorter acting anesthetic, is as effective in blocking circumcision stress as lidocaine, but, because of its shorter plasma elimination half-life and time of onset of action, is safer. Five groups of 15 neonates were matched for weight, age, and Apgar scores and randomly assigned to a control group, one lidocaine group and three chloroprocaine groups with 2-, 3- and 5-minute postinjection waiting periods. Each neonate was subjected to six events during circumcision for which heart rate, tissue oxygenation, and cry duration were recorded. We found that, as in previous investigations, DPNB with lidocaine was effective in reducing neonatal stress, as was evident from decreased excursion from baseline heart rate, tissue oxygenation, and cry duration when compared with the control group (nonblocked). Furthermore, chloroprocaine DPNB approximates the effectiveness of lidocaine, as was evident from decreased change from baseline cry duration, tissue oxygenation, and heart rate during the most stressful events, particularly in the 3-minute wait chloroprocaine group. This more rapid onset of regional anesthesia decreases DPNB circumcision time and benefits patients, parents, and physicians.