To investigate changes in volumes of extraocular muscle (EOM) compartments in unilateral superior oblique (SO) palsy using magnetic resonance imaging (MRI).High-resolution, surface-coil MRI was obtained in 19 patients with unilateral SO palsy and 19 age-matched orthotropic control subjects. Rectus EOMs and the SO were divided into two anatomic compartments for volume analysis in patients with unilateral SO palsy, allowing comparison of total compartmental volumes versus controls. Medial and lateral compartmental volumes of the SO muscle were compared in patients with isotropic (round shape) versus anisotropic (elongated shape) SO atrophy.The medial and lateral compartments of the ipsilesional SO muscles were equally atrophic in isotropic SO palsy, whereas the lateral compartment was significantly smaller than the medial in anisotropic SO palsy (P = 0.01). In contrast to the SO, there were no differential compartmental volume changes in rectus EOMs; however, there was significant total muscle hypertrophy in the ipsilesional inferior rectus (IR) and lateral rectus (LR) muscles and contralesional superior rectus (SR) muscles. Medial rectus (MR) volume was normal both ipsi- and contralesionally.A subset of patients with SO palsy exhibit selective atrophy of the lateral, predominantly vertically acting SO compartment. Superior oblique atrophy is associated with whole-muscle volume changes in the ipsilesional IR, ipsilesional LR, and contralesional SR; however, SO muscle atrophy is not associated with compartmentally selective volume changes in the rectus EOMs. Selective compartmental SO pathology may provide an anatomic mechanism that explains some of the variability in clinical presentations of SO palsy.