1. Glucose and inosine transport by erythrocytes from new-born lambs and adult sheep were compared. Uptake of both permeants was considerably faster in the new-born. Inosine uptake by erythrocytes from nucleoside-permeable and impermeable lambs were not significantly different at birth. The difference between the two phenotypes was first apparent 30 days after birth.2. The post-natal changes in glucose and inosine transport activity closely paralleled the progressive decrease in the percentage of fetal erythrocytes (i.e. cells containing fetal haemoglobin) in the circulation. Cell fractionation studies confirmed that the permeability changes were directly related to changes in the relative proportions of fetal and adult haemoglobin containing erythrocytes.3. The results demonstrate that fetal cells are highly permeable to both glucose and inosine. These cells are replaced by erythrocytes which contain adult haemoglobin and which have a much lower, but still significant, glucose permeability and either low or negligible inosine transport activity depending on the genotype of the animal.4. Inosine transport by fetal erythrocytes from both nucleoside-permeable and impermeable animals was mediated by a nucleoside transport system which had similar properties to that responsible for nucleoside transport in adult nucleoside-permeable cells. Glucose transport in both fetal and adult cells was highly stereo-specific, indicating the presence of a selective transport system.5. It is suggested that the regulatory mechanism responsible for initiating the switch from fetal to adult haemoglobin synthesis may also be responsible for the changes in glucose and nucleoside transport activity.