The co-existence of two mannose-6-phosphate receptors (CD-MPR and Cl-MPR) in most cell types is still a dilemma to be resolved. In this study, some parameters were measured to explore lysosomal apparatus evolution in rat liver during perinatal development, and establish a possible involvement of CD- and/or Cl-MPR in lysosome maturation. Activity of four acid hydrolases was measured in the whole organ at different ages and it was found that N-acetyl-beta-D-glucosaminidase (NAG), beta-galactosidase, and beta-glucuronidase change during development, reaching a peak at the 10th (lay after birth. These results Correlated with the expression and binding properties of CD-MPR previously reported. We also used a method that recognizes phosphomannosylated ligands by using purified biotinylated CI-MPR as a probe, and found that the highest concentrations of ligands also appear around the 10th day. Binding assays were also carried Out, incubating endogenous NAG from 10-day-old and adult rats with membranes from their respective ages, and the results indicated that cation-dependent mannose-6-phosphate receptor (CD-MPR) has more impact on trafficking of the enzyme at the 10th day after birth. We concluded that lysosome maturation in the rat liver occurs around the 10th day after birth, and that the CD-MPR may participate in that event. (c) 2006 Elsevier Inc. All rights reserved.