The molluscicidal activity of Zygophyllum simplex plant leaves powder on Biomphalaria alexandrina and Bulinus truncatus snails after 24 hours of exposure was evaluated under laboratory conditions. The results obtained indicated that the LC$o values for this plant were 42 ppm and 38 ppm and LC90 values were 65 ppm and 60 ppm for B. alexandrina and B. truncatus respectively. The sublethal concentrations (LCo, LCio and LC25) were 4.2, 27 and 34 ppm for Z?. alexandrina and 3.8, 25 and 32 ppm, for B. truncatus. Continuous maintaining of snails in sublethal concentrations (LCo, LCto and LC25) of Z simplex led to an increase in mortality rate of the snails which was significantly higher than that of the control group. The effect of the tested sublethal concentrations of Z simplex on infection of B, alexandrina with 5. mansoni miracidia was studied. The infection rate was significantly lower than that of control snails with reduction rates of 23.5%, 35.1% and 66.9% for snails exposed to LCo, LCjo and LCis, respectively. Prepatent period of exposed snails to LCo, LC10 and LC25 of Zygophyllum was prolonged to be 30.2 ± 2.4, 32.4 + 2.1 and 34.6 ±3.1 days compared to 28.6 ±3.6 days for the control group. Meanwhile, the duration of cercarial shedding was significantly shortened, being 22.8 ± 4.4, 18.3 ±4.9 and 10.5 ± 3.8 days for LCof LQo and LC25 respectively, compared with 44.2 ±4.8 days for the control snails. Highly significant reductions of total cercarial production per snails and per stimulant were also detected in experimental snails in comparison with the control group.