In hypertrophic pyloric stenosis, the muscle is typically described as hypoechoic on sonography. However, we have frequently noted a nonuniform pattern; the pyloric muscle seen in the transverse plane is more echogenic in the near and far fields and less echogenic on the sides. The muscle also appears almost as echogenic as the liver on midline longitudinal sonograms. To establish the frequency of these findings, we reviewed the sonograms of 71 infants with hypertrophic pyloric stenosis. The muscle was imaged directly during surgery in three patients. In an in vitro experiment, muscle arranged to stimulate the pyloric ring was scanned in a water bath. Then, using two sections of muscle, we compared the echogenicity when scanning in a plane perpendicular to the long axis of the muscle fibers with that seen with the beam parallel to the long axis of the muscle fibers. In the transverse plane, nonuniform echogenicity of the pyloric muscle was seen in 59 (98%) of 60 patients. In the midline longitudinal plane, the muscle was equal to or slightly less echogenic than the liver in all patients. Both the in vivo and in vitro studies show that the echogenicity varies with the relationship of the ultrasound beam to the orientation of the circular muscle fibers; this phenomenon is known as the anisotropic effect. Our results show that nonuniform echogenicity of the hypertrophied pyloric muscle is a characteristic sonographic finding caused by the anisotropic effect, which is related to the orientation of the ultrasound beam with respect to the circular fibers of the pyloric muscle.