This study shows that, in control and transgenic mice, there is a parallel increase in LCAT activity and plasma apo A-I concentrations during postnatal development. We also demonstrate that human apo A-I is a much more efficient activator (1.6-fold) of mouse LCAT activity than mouse apo A-I. We propose that the differences in amino acid sequence between human and mouse apo A-I may account for the higher LCAT activity with human apo A-I.