The distribution and phenotypic characterization of T cell receptor (TCR) gamma-delta-cells in human liver tissue was investigated immunohistochemically at light and electron microscopic levels. In chronic liver disease, there was a significant increase in the number of TCR gamma-delta-cells and in the percentage of TCR gamma-delta-cells to CD3+ cells in the portal areas and hepatic sinusoids. Hepatic TCR gamma-delta-cells were classified as small or large gamma-delta cells. Large gamma-delta-cells were increased in chronic liver disease, whereas both small and large gamma-delta-cells were increased in the portal areas and hepatic sinusoids in liver cirrhosis. The increased TCR gamma-delta-cells were of the BB3+ (peripheral) type, indicating that TCR gamma-delta-cells in the liver were of the same lineage as those in the peripheral blood. In addition, the majority of the TCR gamma-delta-cells in the portal areas of liver cirrhosis patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed that the large gamma-delta-cells were lymphoblastoid and contained multivesicles. The present study clearly demonstrated that there are two types of TCR gamma-delta-cells, and that these cells were significantly increased in the livers of patients with chronic liver disease. This suggests that they may be involved in regulation of the immune response and hepatocellular damage in chronic liver disease.