Effects of fluoride on the levels of Lipid peroxidation (LP) and antioxidant enzymes in the brain regions of protein undernourished (PU) and well-fed rats (WF) rats exposed to 100 ppm fluoride in drinking water were investigated. The results indicate that the mean body weights and the total brain weights of PU rats as well as those given fluoride (both WF and PU) were significantly (P < 0.05) lower than their respective controls. The weights of different brain regions were also significantly reduced (P < 0.05) in PU rats compared to WF rats except in the brain stem. Fluoride ingestion diminished the weights of WF and PU rats affecting the cerebrum only (in the case of PU rats) and the cerebellum of both WF and PU rats without an effect on the brain stem of both WF and PU. Additionally, increased LP was observed in the cerebrum and cerebellum of PU rats but after fluoride ingestion, 30% increase in LP was observed only in the cerebrum. In the brain stem however, protein undernutrition was accompanied with a significant reduction in LP but the region seems insensitive to fluoride. There were significant reductions (P < 0.05) in CAT, SOD and GSH in all the brain regions (except the GSH level in the brain stem only) of PU rats. Fluoride induced reduction in the activity of CAT in the three brain regions and on SOD activity in cerebrum only for WF rats but no effect of fluoride on all the antioxidants studied in the three brain regions for PU rats. It is concluded that WF and PU rats responded differently to fluoride toxicity. However, it seems that at the dosage used, fluoride toxicity may be a direct effect on the antioxidant enzymes.