In the present investigation an attempt was made to ascertain whether nonviral liver impairment in rats affects the THelper/TSuppressor ratio. Two hepatotoxic agents were used: (i) galactosamine (GA), which causes a drug-induced hepatitis-like damage, and (ii) orotic acid (OA), which induces fatty changes. Since these two substances act as antidotes to one another they were administered to rats either separately or simultaneously. GA caused severe liver damage documented by a 104-, 48-, and 1.6- fold rise in the plasma concentrations of ALT, AST, and ALP and by multiple foci of hepatocyte necrosis. This was followed by a drop in TH/TS ratio from 2.25 observed in the controls to 0.89 in the GA-treated rats. All of these phenomena were prevented by concurrent administration of GA and OA. OA alone did not show an effect on the liver with respect to changes in plasma enzyme concentrations and by light microscopic analysis. However, OA caused a drop in the TH/TS ratio from 2.25 to 1.55. Neither GA nor OA produced a change in TH/TS ratios in in vitro experiments.