Water content and specific gravity were measured in the cervical, high thoracic, thoracic, and lumbar segments in an experimental model of neoplastic epidural spinal cord compression in rats harboring a thoracolumbar tumor. Increased content of water was observed only in the compressed lumbar cord segments of paralyzed rats (P<0.04). A progressive increase in specific gravity values of the compressed segments accompanied the increasing severity of neurological dysfunction (P< 0.003 in paraplegic rats). Electron microscopy of the compressed cord revealed enlarged interstitial spaces, myelin breakdown, and extravasated blood cellular elements. Treatment with dexamethasone (10 mg/kg q 12 hr x 3) failed to reduce the increased content of water, but corrected specific gravity changes. Treatment with indomethacin (10 mg/kg q 12 hr x 3) reduced both elevated water content and specific gravity values back to normal levels. In untreated animals, the interval between the first neurological sign (limb tail) and paraplegia was 2.8 ± 0.34 days (mean ± SE). Treatment with dexamethasone lengthened this period by 28.6% (P<0.05); treatment with indomethacin lengthened it by 66.4% (P<0.005). We conclude that, because the specific gravity measurements in this model reflect complex pathophysiological processes, their translation into water content values is not advisable. Pharmacological intervention with indomethacin compares favorably with dexamethasone in reduction of spinal cord edema and in delaying the onset of paraplegia.