To determine the effect of 1.5 mL 2% mepivacaine, 0.75 mL 2% mepivacaine, and a combination of 0.75 mL 2% mepivacaine with epinephrine (1:200,000 solution) administered over each palmar digital nerve (PDN) to 6 horses with naturally occurring lameness caused by digital pain. In a crossover study design, 6 horses with forefoot-related lameness were randomly assigned to 1 of 3 groups. Each group received, on different study days, a PDN block using 1.5 mL of 2% mepivacaine, 0.75 mL 2% mepivacaine, or 0.75 mL of a combination of 2% mepivacaine and epinephrine (1:200,000 solution) injected over each nerve. The horses' gait while trotting was analyzed with an inertial, sensor-based motion-analysis system immediately before treatment. The assigned treatment was then administered to the lame forelimb, after which the gait was reevaluated at 5-minute intervals for 15 minutes. All 3 treatments significantly reduced lameness scores at all gait evaluations, but the effect of treatment on the lameness score did not differ significantly among treatments. 0.75 mL of mepivacaine hydrochloric acid injected over each PDN was as effective as twice that volume in decreasing the lameness score of horses with digital pain. The 0.75-mL solution of mepivacaine/epinephrine injected over each nerve did not significantly improve the anesthetic effect of mepivacaine. For a palmar digital nerve block, a lower-than-commonly-recommended volume of 2% mepivacaine effectively ameliorates digital pain. This finding invites investigation as to whether administering a low volume of local anesthetic will more precisely localize pain.