Peganum harmala is plant known since the first century A.D. and still, currently used for therapeutic purposes. Harmaline, the active principle of the plant seeds, and its derivatives, cause visual troubles, loss of coordination, agitation and delirium, and, at high doses, it can produce paralysis. The present study was initiated to evaluate the use and manipulation of therapeutic doses of aqueous extract of P. harmala. Wistar rats were orally dosed acutely and the LD(50) obtained was 2.70+/-0.05g/kg. In chronic studies aqueous extract of P. harmala administered orally for six times a week at doses of 1, 1.35 and 2g/kg during 3 month period increased transaminases. Changes in glucose and creatinine were not significant. No significant gross changes were found at necropsy. Histologic study showed liver degeneration and spongiform changes in the central nervous system (CNS) in rats treated with 2g/kg dose but not at the therapeutic dose of 1g/kg.