Synchronous neural activity causes an extracellular alkaline transient (AT) in a variety of preparations [1]. This pH change is especially robust in hippocampus, and has been shown to boost synaptic NMDA receptor responses [2]. The main hypothesis for the mechanism underlying the AT is that depolarization-induced Ca²⁺ influx activates the plasma membrane Ca²⁺-ATPase (PMCA), which exchanges intracellular Ca²⁺ for extracellular H⁺ [3]. Activation of the PMCA should increase surface pH, as has been demonstrated on snail neurons [3] and retinal cells of the catfish [4]. We sought to determine: (a) if such a rise in surface pH could be detected on neurons in mouse hippocampal slices, and (b) if this surface AT could explain the large extracellular ATs evoked by synchronous activity. This was made feasible by the use of high-speed, low-noise, concentric pH microelectrodes [5] placed against the surface of single CA1 pyramidal neurons, voltage clamped (to -60 mV) by a second pipette. The carbonic anhydrase inhibitor benzolamide (BZ; 10 µM) was included in the saline to maximize surface ATs. Using 20 mV steps, hyperpolarizing the cell to -120 mV did not affect surface pH. Depolarizing the cell to +40 mV caused a rapid AT, which peaked at 0 mV (0.02 ± 0.002 unit pH (mean ± SEM); n=5). The changes recorded with the pH electrode were never seen when it was replaced by a 2M NaCl-filled micropipette, and were markedly reduced by adding a small amount of HEPES buffer, indicating that the electrode responses represented pH changes. Addition of 1, 5, or 20 mM HEPES reduced the AT by 43 ± 7.3, 91 ± 5.7, and 98 ± 1.6%, respectively (n=5 and p<0.01 (paired t-test) for all). In experiments where BZ was not added to control saline, a small surface AT was evoked (0.01 ± 0.002 unit pH, n=5), and was increased by 356 ± 100% (p<0.02) after addition of BZ. Addition of Cd2+ (300 µM) reduced the surface AT by 71 ± 14% (n=6; p<0.002). Bath addition of the PMCA inhibitor 5(6)-carboxyeosin (CE; 200 µM) reduced the surface AT by 65 ± 14% (p<0.05). Addition of CE (0.5 µM) to the patch pipette reduced the AT by 88 ± 7.5% five min. after breakthrough to whole cell mode (n=5; p<0.05), whereas the response remained stable for more than 5 min. without intracellular CE (n=5; p=0.28). To simulate the response to repetitive antidromic stimulation, a 2 sec 100 Hz spike train was used as the voltage clamp command. This elicited a similar surface AT that was inhibited 71 ± 19% by bath addition of CE. By contrast, real antidromic stimulation of the CA1 pyramidal neuron population elicited an extracellular AT that was not inhibited by bath-applied CE (n=7 slices). These results indicate that while activation of single pyramidal neurons evokes the anticipated CE-sensitive rise in surface pH, the AT elicited by synchronous activity cannot be similarly attributed to the neuronal PMCA.