Engraftment of intramuscularly transplanted myogenic cells in mice can be optimized after induction of massive myofiber damage that triggers myofiber regeneration and recruitment of grafted cells; this generally involves either myotoxin injection or cryodamage. There are no effective methods to produce a similar process in the muscles of large mammals such as primates. In this study, we tested the use of intramuscular electroporation for this purpose in 11 macaques. The test sites were 1 cm³ of skeletal muscle. Each site was treated with 3 penetrations of a 2-needle electrode with 1 cm spacing, applying 3 pulses of 400 V/cm, for a duration of 5 milliseconds and a delay of 200 milliseconds during each penetration. Transplantation of β-galactosidase-labeled myoblasts was done in electroporated and nonelectroporated sites. Electroporation induced massive myofiber necrosis that was followed by efficient muscle regeneration. Myoblast engraftment was substantially increased in electroporated compared with nonelectro-porated sites. This suggests that electroporation may be a useful tool to study muscle regeneration in primates and other large mammals and as a method for increasing the engraftment of myoblasts and other myogenic cells in intramuscular transplantation.