To determine if the sex differences in clearance of long chain fatty acids by the liver observed in the rat are relevant to humans, the authors isolated hepatocytes from human adult males and females (five per group) and measured the initial (unidirectional) clearance of [3H]-palmitate from buffer containing albumin. The clearance was significantly higher (about twofold) in hepatocytes from females because of a higher permeability of the plasma membrane to the fatty acid. The livers had been perfused with University of Wisconsin (UW) solution and stored for 12-16 h before isolation of the cells. The magnitudes of the clearances in humans were similar to those in the rat when the livers were stored similarly, but lower than in cells isolated from fresh rat liver. When hepatocytes isolated from fresh rat liver were stored in UW solution, clearance of [3H]-palmitate was unaffected. Thus, hepatocytes prepared from intact liver stored for several hours in UW solution do not have as good preservation of function as hepatocytes isolated from fresh liver and then stored in UW solution.