The objective of this study was to alter biomechanical forces generated by the muscles of mastication that affect the growth of the craniofacial skeleton through the implantation of neurotransmitter microspheres to stimulate trigeminal motoneurons (TMNe) in vivo. Polyanhydride microspheres containing L‐glutamate were stereotaxically implanted 170–920 μm rostral to the left‐side trigeminal motor nucleus (TMNu) in 17 Sprague–Dawley rats at 33–38 days old. Seven rats received blank‐microsphere implants and two rats had empty delivery system penetration as controls. All rats were killed 10–14 days postsurgical for dissection, brain histology, osteometric data, and SEM analyses. Dimensions of the facial skeletons of glutamate‐microsphere rats showed significant (P<0.01, P<0.05) differences when compared to control animals. Glutamate‐microsphere animals also demonstrated significant (P<0.01) differences between the dimensions of their implant‐and nonimplant‐side facial skeletons. SEM analyses indicated that glutamate‐microsphere rats had greater implant‐side wear of their mandibular incisors compared to blank‐microsphere or delivery system controls. The skeletal alterations in the glutamate‐microsphere rats are hypothesized to be due to increased implant‐side TMNe and masticatory muscle activity patterns.