Focal hepatocellular hyperplasia and focal mixed (hepatocytes and sinusoidal cells) hyperplasia are early histological alterations indicative of vinyl monomer exposure. To evaluate their uses in screening chemical workers, 93 liver biopsy specimens from 78 persons were examined in double-blind duplicative fashion. Forty-eight specimens were from exposed chemical workers, 35 of them having liver biopsy(ies) for hepatic test abnormalities and 13 for nonliver-related reasons. A comparison group consisted of 30 nonchemical workers who had undergone liver biopsy for nonliver related reasons. Twenty-three of the exposed workers (48%) had hepatic lesions consistent with exposure: 17 (35%) of these had focal hepatocytic hyperplasia, while 6 (13%) had focal mixed hyperplasia or more advanced lesions. Only five of the comparison group had like findings: four (13%) had focal hepatocytic hyperplasia; one had focal mixed hyperplasia and sinusoidal dilatation. This individual had persistent hepatic test abnormalities with the focal mixed hyperplasia and a sinusoidal dilatation, and on subsequent biopsy, angiosarcoma (and a history of using hair spray containing vinyl chloride propellant). Ten individuals had 25 multiple biopsies also read double-blindly; 10 had two or more readings of the same biopsy. Duplicate 21 of 23 (91%) and multiple 27 of 28 (96%) biopsy interpretations in the same individual were identical. Only 6% of either duplicate and/or multiple readings disagreed. Both focal hepatocellular and mixed hyperplasia were always associated with abnormalities in hepatic test results of which indocyanine green clearance was the most sensitive and γ-glutamyl transpeptidase the least specific. Focal hepatocellular hyperplasia is a more common finding and occurs earlier than the focal mixed hyperplasia among vinyl monomer exposed workers. Follow-up for 5 to 7 years yielded no biochemical or histological evidence of spontaneous progression of this lesion in a work environment where vinyl chloride levels were 10 ppm with time-weighted averages of 1 to 2 ppm. Focal mixed hyperplasia is, as noted, a later and less frequent finding among vinyl monomer-exposed workers. Some individuals with this lesion develop hepatic angiosarcoma independent of subsequent vinyl monomer exposure. In screening for chemical liver injury, indocyanine green clearance supplementary to routine tests is recommended with confirmation by liver biopsy.