Alcohol abuse is known to cause disturbances to iron homeostasis in man and is associated with elevated serum ferritin levels. We have previously shown that ethanol metabolism in the rat hepatocyte is associated with an immediate reduction in ferritin uptake by this cell. In this study we have examined the effect of pair-feeding the Lieber-DeCarli liquid alcohol diet on ferritin uptake by rat hepatocytes. Rat liver ferritin was radiolabeled with 59Fe in vivo and isolated by conventional techniques. Rats were pair-fed the Lieber-DeCarli liquid alcoholic diet for 4-6 weeks. Hepatocytes, isolated from their livers by collagenase perfusion, were incubated with [59Fe]ferritin in L-15 medium at 37 degrees C and 4 degrees to measure ferritin uptake and binding. The in vitro effect of ethanol on these hepatocytes was also studied. Ferritin and iron parameters were measured in the sera and hepatocytes of these animals and a comparable group of normal chow-fed rats. The rate of ferritin uptake by hepatocytes from alcohol-fed rats was significantly faster than that of their pair-fed controls (0.743 +/- 0.061 vs. 0.540 +/- 0.042 ng/min/10(6) cells, p < 0.05). However, the rats on Lieber-DeCarli control diet exhibited a lower hepatocyte ferritin uptake rate than chow-fed animals (79.3 +/- 8.1% of the control values, p < 0.01). In vitro incubation of cells in 100 mM ethanol resulted in less inhibition of ferritin uptake by hepatocytes from alcoholic rats than from their pair-fed controls (11 +/- 7.1% inhibition vs. 43.6 +/- 10.7% for controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)