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The effect of ethylene thiourea (ETU) upon liver cells was evaluated in male Sprague-Dawley rats. ETU was administered ad libitum in drinking water at concentrations of 1, 5, 50, and 500 ppm for time intervals of 1, 2, and 5 days, 1 and 2 weeks, 1, 2, 4, and 8 months. Two additional groups of control animals received ETU-free drinking water or a diet supplemented with 0.06% 3-MeDAB. Electron microscopic evaluation of tissue samples could detect no changes in liver cell morphology of rats receiving 1, 5, or 50 ppm ETU for up to 8 months. By contrast, rats receiving 500 ppm ETU exhibited alterations in hepatic cell morphology after 4 months of exposure. These alterations included a dramatic increase in the amount of smooth endoplasmic reticulum (SER) with a concomitant reduction in rough endoplasmic reticulum (RER), and a relocation of microbodies and mitochondria to the periphery of the SER. No alterations were seen at the shorter time intervals. These changes probably represent a response to the sustained ingestion of high concentrations of highly toxic materials and most likely do not represent a specific response to ETU. No tumors were detected in any of the samples examined or in controls receiving ETU-free drinking water. Animals receiving 3-MeDAB in their diet all developed hepatic tumors within 4 months.