A case of enalapril-induced acute hepatotoxicity with an unusual morphology is described. This morphology was characterized by macro- and microvesicular steatosis associated with neutrophil infiltration and Mallory bodies, occasionally with satellitosis. These alterations were most abundant in zone 1 of the periportal region, less common in zone 2 and rare in zone 3. There was also confluent periportal necrosis with sinusoidal fibrin deposits associated with intense ductal metaplasia and an infiltrate of inflammatory cells that included plasmocytes and a few eosinophils, as well as focal biliary damage. This morphology, that may be referred as "predominantly periportal steatohepatitis", was distinct from that associated with non-alcohol and alcohol-induced steatohepatitis, both initiated in acinar zone 3 and subsequently extended to other zones.