OBJECTIVES: Although the effectiveness of gamma knife radiosurgery (GKRS) in controlling the size of pituitary adenomas has been well demonstrated in many studies, the time period in which significant changes in tumor size occurs has been investigated in a limited fashion. It is important to determine the therapeutic window of GKRS in treating pituitary adenomas, i.e., the effective timeframe during which significant size reduction of these tumors occurs, so that alternative treatments such as further GKRS or microsurgery might be prescribed in a timely manner if clinically indicated. METHODS: This was a nested sample of an ongoing local cohort study on GKRS for pituitary adenomas at the University of Virginia. Magnetic resonance imaging (MRI) using dedicated sequences was employed. Only patients with a baseline MRI (TP0) and at least 1 follow-up study performed in the University Hospital after GKRS were included. The follow-up scans were performed at five time-points (TP1-TP5) which were 6, 12, 24, 36 and 48 months after GKRS. The dimensional indices of the tumors were measured in three orthogonal planes, i.e., transverse (TR), antero-posterior (AP) and cranio-caudal (CC). The volumes of the tumors were estimated by using the following formula: [Formula: see text]. Tumor volume decrease by more than 25 % from baseline was considered as 'shrinkage',