Ribosome inactivating proteins (RIPs) are a family of proteins produced by plants, bacteria and fungi. RIPs have specific N-glycosidase activity, and they cleave a specific glycosidic bond in a universally conserved stem and loop structure within the large ribosomal RNA of all organisms. Saporin, a cytotoxic RIP from the plant Saponaria officinalis has been earlier shown to manifest its cytotoxicity by a combination of its N-glycosidase and apoptosis inducing activities. Saporin, along with many other RIPs also has strong inhibitory activity towards HIV integrase. In the current study, using two in vitro model systems, it is established that saporin inhibits propagation of HIV-1 in host cells. Saporin also showed a potent anti-HIV-1 integrase activity in vitro. Using three active site mutants of saporin, which respectively lack N-glycosidase, apoptosis inducing or both activities, it is shown that saporin's in vitro anti-HIV-1 integrase activity is independent of its N-glycosidase activity. However, for the anti-HIV activity of saporin, the apoptosis inducing activity is important.