We used the clearance ratio test to determine whether the presence of albumin enhances the uptake of palmitate by hepatocyte monolayers. If uptake is facilitated, then the ratio of palmitate clearance by hepatocytes in the presence of 600 and 300 microM albumin (i.e., Clt600/Clt300) will exceed the square root of the ratio of the unbound fractions at 600 and 300 microM albumin (i.e., square root of alpha 600/alpha 300). The latter value was determined using the heptane-water partitioning technique. The hepatocyte clearance ratio (0.92 +/- 0.06) exceeded the predicted value (0.80) by 15% (p < 0.05). The observed clearance rate also exceeded that predicted by the diffusion-reaction model.