The base exchange enzymes and phospholipase D represent a group of enzymes which alter the polar portion of phospholipids. The base exchange enzymes provide a mechanism of inter-converting different species of phospholipids whereas phospholipase D hydrolyzes these phospholipids to phosphatidic acid. Although the occurrence of these activities is widespread, this article is restricted to a description of the mammalian enzymes.Originally it was believed that these catalytic activities resided in a single enzyme. As a result of successes in partial purifications and separations it is clear that separate enzymes exist for the exchange of serine, for the exchange of choline, and for the exchange of ethanolamine resulting in their appearance in the corresponding phospholipid. These enzyme activities are not a reflection of phospholipase D action. Conversely, a partially purified phospholipase D from rat brain was devoid of detectable base exchange activity. However, this enzyme preparation possessed transphosphatidylation activity producing phosphatidylglycerol from glycerol and lecithin.These enzymes are presumed to be functionally significant for cellular homeostasis; however, strong evidence supporting this contention is unavailable. The base exchange enzymes appear to be concentrated in the "microsomal" fraction of tissues. The choline base exchange enzyme is located on the cytoplasmic surface while the serine and ethanolamine base exchange enzymes are located on the luminal surface of the endoplasmic reticulum of rat brain tissue. The lipid environments in which the individual enzymes reside are also distinctly different suggesting that their in situ domains within the microsomal membrane are dissimilar. Therefore it appears that the enzymes are distinctly separate catalytic entities. They also are in topographically different locations on the microsomal membrane and reside in different lipid environments as well. These observations would imply functionally distinct roles for the separate enzymes. Evidence is available which suggests that their existence might be demonstrable in vivo.