Seven patients with rheumatoid disease were given the iron-chelating drug desferrioxamine (DFX) to evaluate its possible anti-inflammatory effects. Two of these patients, who also received the anti-emetic prochlorperazine, lost consciousness for 48-72 h and then fully recovered. Electroencephalography showed abnormalities of the type associated with metabolic disturbance. One of these patients showed pyramidal features and subsequently developed an optic neuropathy and pigmentary retinopathy. Analysis of his cerebrospinal fluid showed a decrease in loosely-bound (catalytic) iron and increase in loosely-bound (catalytic) copper, total iron and products of lipid peroxidation, with values approaching normal as the symptoms resolved. Subsequent in vivo/vitro studies clearly demonstrated that the neurological effects were due to a synergistic action of desferrioxamine and prochlorperazine, probably resulting in exceptional fluxes of intra/extra cellular iron/copper disturbing noradrenergic and serotonergic systems. Two other patients who did not receive prochlorperazine, developed retinal problems which later improved, one after only 15 g of desferrioxamine. Our observations suggest a new model for metabolic encephalopathy studies and provide insight into the mechanisms of pigmentary retinopathy.