The oral administration of 150 mg/kg/day of the drug RMI 14,514 (5-tetradecyloxy-2-furancarboxylic acid) to rats for 4 months resulted in a significant reduction in plasma total and esterified cholesterol, an effect more pronounced in males. After 1 month of treatment, fine structural alterations of hepatocytes first appeared as vacuoles within the matrix of the microbodies. Microbodies lacking these changes frequently exhibited one of three types of tubular formations which were of variable diameter: the most common, type 1 (690–790 Å); type 2 (370–460 Å); type 3 (1480–1680 Å). Relative to the microbody limiting membrane, these tubules were either external (types 1 or 3) or internal (type 2) and frequently protruded in apposition to other organelles. The microbodies also increased in number as well as size after 1 week of treatment with 150 mg/kg/day of RMI 14,514. Dosages of 100 or 200 mg/kg/day for 6 months produced additional findings of focal hyperplasia of the smooth and rough endoplasmic reticulum. Following a 1-month recovery period, hepatocytes from rats previously treated with a 150-mg/kg/day dosage for 4 months had a fine structure similar to controls, indicating a reversibility of drug-induced alterations.