Repeated incubation of Plasmodium falciparum culture in 0.015 % saponin solution for a total of 35 min destroys most of the uninfected cells, leaving only the ring-infected erythrocytes (RIEs). Parasites concentrated by this method can subsequently complete the asexual cycle and infect other erythrocytes. It is possible that resistance to saponin is mediated by one or more of the numerous parasite proteins present in the host erythrocyte membrane. We have found that schizonts are as susceptible as uninfected erythrocytes to saponin, indicating that the protective protein is parasite stage specific. Studies with cultured parasites have shown that ring-infected erythrocyte surface antigen (RESA) strengthens host erythrocyte membrane and protects against destruction. Therefore, we hypothesize that RESA could be involved in resistance to saponin. Here, we have carried out PCR test on RESA gene, using three different primers. One of them showed that P. falciparum isolates collected directly from infected humans and cultured only for a few days, or not at all, have amplicon sizes ranging from 372 to 510 bp. However, the amplicon size changed to 873 bp when in vitro growth was continued for one or more weeks. This genetic transformation precedes acquisition of the ability to confer saponin resistance to RIEs.