The time-course of plasma lipid alterations and of triglyceride accumulation in the liver was investigated in male and female rats 12, 24 and 48 hours after treatment with 3.48 mmole/kg (0.75 g/kg) D-galactosamine (Ga1N). In the early stages of Ga1N-induced liver injury the concentrations of triglycerides, phospholipids and total cholesterol decreased, while in the later stages these values in the plasma increased above normal, especially in male animals. In contrast, glucose concentrations continually decreased, while free fatty acid (FFA) levels rose to twice those normal in female animals. Male animals had significantly lower FFA-values throughout the experiment. Consistently, the triglyceride accumulation on liver was 75 mg/g in female animals 24 hours after Ga1N administration, while male animals in the average showed only 33 mg/g triglycerides. Similar fatty infiltrations were obtained in female animals with the rather low doses of 1.16 and 2.32 mmol/kg Ga1N. It is concluded that the increase of FFA-influx after Ga1N administration is the main cause for fatty infiltration, the sex differences in the plasma FFA concentrations explaining the net differences in liver triglyceride accumulation. Additional effects in the pathogenesis of fatty liver might stem from disturbed glycosylation reactions and/or an altered secretion and metabolism of lipoproteins after Ga1N-induced liver injury.