Rats were given a lithium-containing diet (40 mmol/kg) to study the effect of lithium on the structure of collecting ducts from the inner stripe of the outer medulla. The results show that there is a significant increase in the volume density of collecting ducts already after one week on this diet. The volume density of both intercalated and principal cells increases, whereas the volume density of mitochondria in the cytoplasm increases in the intercalated cells only. The increased volume of both principal and intercalated cells seems to be part of a general hyperplasia and hyperactivity of the collecting duct, which may in some way be related to the effects of lithium on vasopressin-mediated mediated water transport. The specific changes in the intercalated cells may be a consequence of the effects of lithium on distal nephron potassium and hydrogen ion transport in the distal nephron.