The developmental changes in apoAI expression in human apolipoprotein AI (apoAI) transgenic and nontransgenic control mice and the effect of these changes on high density lipoprotein (HDL) sizes were investigated. Results demonstrated that both human and mouse apoAI mRNA levels sharply increased following delivery and then decreased prior to weaning. Unlike the changes in apoAI mRNA, plasma apoAI concentration and HDL mass increased following delivery and remained elevated as the animals matured. In these animals, parallel increases in plasma apoAI and HDL mass with development were accompanied by increases in HDL particle sizes. Control mice demonstrated a monodisperse population of particles that increased in particle size from 7.5 nm (at 2 days prior to birth) to 9.8 nm (at 13 days after birth). The latter is similar to the adult HDL size and distribution. Transgenic mice, unlike controls, exhibited several distinct HDL populations, which also increased in size as animals matured. These results suggest that post-transcriptional factors are important in regulating apoAI plasma levels and that developmental changes in plasma apoAI concentrations are associated with changes in HDL size distribution.