Alternative splicing of a precursor mRNA enables different protein isoforms to be generated from a single gene. A splice variant of the malaria parasite’s ‘chloroquine resistance transporter’ gene (pfcrt) has been identified in parasites isolated from Sudanese patients undergoing treatment with artemether-lumefantrine . This transcript contains an exon 3–4 deletion and would encode a grossly-deformed protein that lacks several of the transmembrane domains of full-length PfCRT. A full-length pfcrt transcript was also detected in the parasite isolates, suggesting that the two transcripts were co-expressed. We have employed the Xenopus laevis oocyte expression system to determine the function of the PfCRT splice variant. The splice variant protein was produced by the oocytes, but did not transport chloroquine (a substrate of full-length PfCRT). Instead, the PfCRT splice variant was observed to downregulate the expression of full-length PfCRT. Moreover, we found that it also downregulated the expression of several unrelated full-length transporters. Previous studies of naturally-occurring splice variants of other eukaryotic transporters present a number of striking similarities with our observations of the PfCRT splice variant. For example, these transcripts were predicted to encode proteins with grossly-deformed topologies and the resulting proteins were unable to transport the substrate(s) of their full-length transporter. Most importantly, these splice variants were found to downregulate the expression of their full-length transporter [2–4]. The similarities between the effects of these splice variants and the PfCRT splice variant suggest that these proteins are acting through a previously-undescribed regulatory mechanism that is conserved in eukaryotes, the nature and biological relevance of which are currently unknown. We have applied a number of in vitro and in situ assays, including the Xenopus oocyte expression system, to characterise the regulatory effects and the mode-of-action of these transporter splice variants. The key findings of these studies will be presented.