The alteration of cellular calcium sequestration has been postulated to be a primary mechanism in the initiation of irreversible cell damage. Crude oil has been shown to cause concentration- dependent inhibition of calcium influx and mitochondrial swelling which may relate to its toxicity. Nigerian 'Bonny' Light Crude Oil (BLCO) is produced in the Niger-Delta region of Nigeria where oil spills are frequent and can endanger human-health, yet BLCO has not been studied in this regard. We have studied the effects of two doses of BLCO on mitochondrial DNA (mt.DNA), cytoplasmic total hydrocarbon concentrations (cyt.THC) and cytoplasmic Ca2+ (cyt.Ca2+) concentrations in livers of adult male guinea pigs exposed by intraperitoneal injection. The results showed that at 2.5 and 5.0 (ml/kg bw), BLCO caused dose-related increases in mt.DNA concentrations (128% and 485%) respectively over the controls, and cyt.THC (47.5% and 100%) respectively; while it caused near-100% decrease in cyt.Ca2+ concentrations (94% and 96.8%) respectively lower than the controls. These results suggest that BLCO caused the increased availability of crude oil hydrocarbons in the liver cells, and subsequent induction of unscheduled mt.DNA synthesis, and alteration of mitochondrial/endoplasmic reticulum Ca2+ sequestration or ca2+ - concentration gradient, leading to the inhibition of Ca2+ influx into the cytosol. These events may explain the probable hepatotoxicity of BLCO.