The ERD2 gene product in mammalian cells and yeast is a receptor required for protein retention in the endoplasmic reticulum (ER); immunolocalization studies indicate that the protein is concentrated in the cis Golgi. We have identified a homologue of ERD2 in the malaria parasite, Plasmodium falciparum (PfERD2). The deduced protein sequence is 42% identical to mammalian and yeast homologues and bears striking homology in its proposed tertiary structure. PfERD2 is tightly confined to a single focus of staining in the perinuclear region as seen by indirect immunofluorescence. This is redistributed by brefeldin A (BFA) to a diffuse pattern similar to that of parasite BiP, a marker for the ER; removal of the drug results in recovery of the single focus, consistent with the localization of PfERD2 to the parasite Golgi and its participation in a retrograde transport pathway to the ER. Sphingomyelin synthesis is a second resident activity of the cis Golgi whose organization is sensitive to BFA in mammalian cells. Within the parasite it again localizes to a perinuclear region but does not reorganize upon BFA treatment. The results strongly suggest that these two activities are in distinct compartments of the Golgi in the malaria parasite.