The adrenal medulla of mammals has a heterogeneous population of cells. In adults most are epithelial cells containing a particular type of cytoplasmic granule. Based on a variety of cytochemical and ultrastructural studies it is now accepted that 2 different adrenal medullary chromaffin cell types can be distinguished, ie noradrenaline (NA) and adrenaline (A) synthesising and storing cells. Other cell types present in the adrenal medulla include neuronal elements comprising either cell bodies or nerve fibres entering from outside the gland (extrinsic innervation). It is assumed that adrenal medullary cells have a limited life span, ie they are replaced after a certain period. Data on this replacement process are scarce. Recently, we initiated an investigation into this question using cytochemical procedures that enable the detection of DNA duplication to measure mitotic activity in individual cells. Female Sprague-Dawley rats aged 22-36 wk received a single ip injection of BrdU or BrdU was administered continuously via an implanted mini-osmotic pump. Cell nuclei that had incorporated BrdU were demonstrated using an indirect immunoperoxidase staining technique. At 1 h after a single injection, 0.46+/-0.07% of the adrenal medullary (chromaffin) cells were labelled. This increased to 0.77+/-0.08% after 12 h with no further increase during the next 7-8 d. With continuous infusion of BrdU the fraction of labelled cells increased gradually to about 40% after 73 d (the longest period studied). These results show that in adult rats adrenal medullary cells are able to divide, although at a slow rate (renewal rate of about 1%/day).