Purpose: This cooperative study was designed to evaluate the safety, MR imaging characteristics and clinical response to intrathecal gadopentetate dimeglumine (GD) administration in human patients. Subjects and methods: This prospective study consisted of fifty-two patients, 32 men and 20 women, ranging from 1 month to 68 years of age (mean age: 42 years). Clinically, patients presented with posttraumatic paraparesis/paraplegia (n=6), headache (n=24), subcutaneous mass (n=2), dementia (n=2), CSF rhinorrhea (n=8), and back pain (n=10). Via lumbar puncture, a single dose of 0.2 ml, 0.5 ml, or 1.0 ml of GD was injected into the subarachnoid space. Immediate and delayed MR imaging (range: 4 to 40 hours) was subsequently carried out on a 1.0-1.5 T magnet. All patients were hospitalized for an observation period of 24 hr after examination. A 6 to 15 month clinical follow-up was also performed. Results: No patient manifested gross behavioral changes, neurologic alterations, or seizure activity. Seven patients experienced headache and two patients had nausea and vomiting. The intrathecal GD enchanced MR myelography/cisternography demonstrated: intervertebral disc herniation (n=5), post-traumatic spinal stenosis (n=5), post-surgical spinal cyst (n=1), myelitis (n=1), intradural/extradural spinal mass (n=2), spinal vascular malformation (n=1), meningomyelocele (n=2), neuroenteric cyst (n=1), ventriculomegally (n=2), cranial arachnoid cyst (n=20), mega cisterna magna (n=1), CSF rhinorrhea (n=8), and postoperative encephalomalacia/cyst formation (n=3). Conclusion: This cooperative study shows the relative safety and feasibility of low dose (1.0 cc or less) intrathecal GD administration in a small group of patients. The potential clinical applications include: the evaluation of obstructions and communications of the subarachnoid space, spontaneous or traumatic CSF leaks, and CSF flow/interstitial CNS parenchymal diffusion dynamics. This worldwide cooperative study seeks to progressively perform additional human studies for further evaluation of the clinical applications and long term safety of this procedure in a larger number of subjects.