The leaves of Erythrophleum africanum is known in the arid land of tropical Africa to posses toxicological properties. Phytochemical, acute and sub-acute evaluation of the possible toxicity risk of E. africanum aqueous leaves extracts were investigated in this study. Phytochemical constituents detected in the leaves extracts were saponins (1.16% w/v), cardiac glycosides, tannins (0.17 true tannins and 0.23% w/v pseudotannins), flavonoid glycosides, free flavonoids and alkaloids (4.34% w/v). The Lethal Dose (LD50) of the aqueous leaves extracts was greater than 3000 mg kg(-1) per os (orally) in albino rats. Sub-acute administration of the extract for 28 days resulted in significant (p<0.05) changes in some renal and liver indices at 3000 and 2000-3000 mg kg(-1) body weight, respectively. Histopathological lesions of the kidney and liver in form of moderate and marked infiltration with necrosis and perivascular lymphocytic cuff were observed. The observed lesions could be due to roles played by liver and kidneys in metabolism of xenobiotics and their elimination from the body. These investigations thus seem to indicate the toxic effects of the aqueous leaves extracts of E. africanum at 2000-3000 mg kg(-1). These could be attributed to the combined toxicity of the phytochemical constituents such as tannins, saponins, glycosides and alkaloids.