The pH-adjustment of local anesthetic solutions with sodium bicarbonate may shorten onset time and improve spread of neural blockade. The authors undertook a prospective, double-masked, randomized study to see if a pH-adjusted mixture of lidocaine, bupivacaine, and hyaluronidase had faster and more complete onset of neural blockade, when used for peribulbar anesthesia. Eighty patients were randomly assigned to four groups and received a peribulbar block with one of four mixtures: group 1 (L) = 2% lidocaine, group 2 (LPH) = 2% lidocaine with 0.06 meq/ml sodium bicarbonate, group 3 (LE) = 2% lidocaine with 1:100,000 epinephrine (commercially prepared), or group 4 (LEPH) = 2% lidocaine with 1:100,000 epinephrine with 0.06 meq/ml sodium bicarbonate. To 5 ml of each of the preceding groups, 5 ml of 0.75% bupivacaine and 150 units of hyaluronidase was added. After each block, extraocular muscle movement was followed in each quadrant until akinesia developed. In the event of incomplete akinesia, blocks were supplemented at 20 minutes. The LPH group had the fastest onset to complete akinesia (7.0 +/- 2.0 minutes, mean +/- SEM) when compared with the onset time of all other groups (group 1 = 11.5 +/- 1.9 minutes, group 4 = 13.1 +/- 1.4 minutes, and group 3 = 16.0 +/- 1.8 minutes, significance greater than 95% by analysis of variance). Furthermore, when compared with group 3 by analysis of variance, group 4 had a faster onset time. The authors conclude that pH-adjustment of solutions with bicarbonate of either lidocaine/bupivacaine/hyaluronidase or commercially prepared lidocaine with epinephrine/bupivacaine/hyaluronidase decreases the onset time of peribulbar anesthesia.