['Lipid molecules may play a regulatory role in the secretory pathway of mammals and yeast. The lipid hydrolase phospholipase D (PLD) is one candidate for mediating regulation of secretion, based on the location of this enzyme and its requirements for activation.', 'We found that primary alcohols, which block formation of phosphatidic acid (PA) by PLD, inhibited the transport of two different viral glycoproteins from the endoplasmic reticulum to the Golgi complex in Chinese hamster ovary cells. Corresponding secondary alcohols, which are much less potent in blocking PA formation, were also less effective in blocking transport of the glycoproteins. The block in glycoprotein transport imposed by primary alcohols was reversed when PA, in the form of liposomes, was exogenously supplied to the culture medium.'] Is phosphatidic acid formation by phospholipase D required for transport from the endoplasmic reticulum to the Golgi complex?