Abstract: Hippocampal formation is involved in learning and memory and has also been reported to be sensitive to neurotoxic insults. However, little has been reported on the chronic simultaneous intake of ethanol and acetaminophen despite their degrees of abuse and misuse as regards hippocampus. In this study, forty adult wistar rats of average weight 150±20.2 g were randomly distributed into four groups of treatments T1, T2, T3 and control C (N = 10). For a period of six weeks, animals in group T1 received 100 mg kg-1 b.wt. acetaminophen and 25% ethanol in 2% sucrose solution while group T2 animals received 25% ethanol in 2% sucrose solution. T3 animals were given 100 mg kg-1 b.wt. acetaminophen and group C animals were given only distilled water. The animals were sacrificed by whole body intracardiac perfusion fixation and the regions of hippocampus were dissected out using Paxinos stereotaxic coordinate method. Brain specimens were processed for routine histological techniques, sectioned at 6 μ and stained for nissl’s substance. Significantly reduced neuronal density (p>0.05) of 44 and 38% neuronal loss in CA3 subfield, respectively in treatment groups T1 and T2 compared to control group was recorded. Also, marked degeneration of pyramidal neurons in the regions of CA1 and CA3 of treatment groups that received 100 mg kg-1 b.wt. acetaminophen and 25% ethanol in 2% sucrose solution as well as animals that received 25% ethanol in 2% sucrose solution, respectively with mild degenerative effects in the group that took 100 mg kg-1 b.wt. acetaminophen compared to the control group was also observed. These alterations observed following exposure to chronic simultaneous administration of ethanol and acetaminophen point to possibilities of higher memory impairments and learning deficits which are of very strong public health concern.