Raised intracranial pressure leads to increased pressure around the optic nerve (ON), which underlies the formation of papilledema and the enlargement of the dural optic nerve sheath (ONS). In clinical practice, the presence of widened ONSs is demonstrable on neuroimaging, but their relationship to cerebrospinal fluid (CSF) pressure remains unknown. The authors investigated the ONS response to pressure during CSF absorption studies in 12 patients undergoing neurological testing. The ONS diameter was evaluated by serial B-mode ultrasound scans of the anterior ON near its entry into the globe. All patients tested showed ONS diameter changes that exhibited covariance with the alteration of lumbar CSF pressure and were completely reversible during the infusion tests. The maximum difference in ONS diameter between baseline and peak pressure conditions was 1.8 mm on average (range 0.7-3.1 mm), corresponding to an average ONS diameter variation of 45% (range 15-89%). Regression analysis yielded a linear covariance between ONS diameter and CSF pressure with different slopes across subjects (0.019-0.071 mm/mm Hg, mean r = 0.78). However, this linear relationship was only present within a CSF pressure interval. This interval differed between patients: ONS dilation commenced at pressure thresholds between 15 mm Hg and 30 mm Hg and in some patients saturation of the response (constant ONS diameter) occurred between 30 mm Hg and 40 mm Hg. With a single exception, definitely enlarged ONS diameters (> 5 mm) were present when CSF pressure exceeded levels of 30 mm Hg. Retrospectively, discrimination between normal and elevated outflow resistance was possible on the basis of the ONS response to intrathecal infusion alone. It is concluded that the human ONS has sufficient elasticity to allow a detectable dilation in response to intracranial hypertension. Because of a variable pressure-diameter relationship, the subarachnoid pressure cannot be predicted exactly by single scans. Therefore, the clinical relevance of this method relies on the demonstration of pathologically enlarged sheaths or ongoing enlargement on serial ultrasonography studies.