Few studies have examined the possible adverse effects that epidural injection of depot corticosteroid preparations may have on meningeal membranes and nervous tissue. Thirty-six healthy adult white rabbits received 0.3 ml/kg epidural injections of either lactated Ringer's solution (negative control group), 1% lidocaine containing methylprednisolone acetate (study group), or normal saline containing talc (positive control group). Animals were killed either 4 or 10 days after injection and stained sections of the spinal cord and meningeal membranes were examined by light microscopy. In all animals that received either lactated Ringer's solution or lidocaine with methylprednisolone acetate, microscopic examination of specimens taken from the L5-L6 interspace revealed no white cell infiltrates and no fibroblastic activity. All animals that received epidural injections of normal saline containing talc had marked infiltration of tissue macrophages in the epidural space. There was no thickening of the meningeal membranes or nerve roots in any animal. The complete lack of inflammatory changes and meningeal thickening demonstrated in this pilot study helps to confirm the safety of methylprednisolone acetate when injected into the epidural space.