The biodegradability of water-extracted saponins of berries from the Endod plant, Phytolacca dodecandra L'Herit, was evaluated under OECD standardized conditions. Persistence of the saponins was evaluated by determination of saponin concentrations in water over a 30-day period, using a quantitative HPLC method and a semiquantitative hemolytic assay, which is considered a potential field method. The two methods were compared. Bioassays were simultaneously conducted using Biomphalaria glabrata fresh water snails to assess the molluscicidal potency over time. All experiments were carried out in water, which was chemically balanced to sustain snails, and to one set river water was added to the medium to mimic natural conditions. (1) Saponin concentrations in water treated with an aqueous extract of P. dodecandra cultivar E44 were stable for 2 days then rapidly decreased during the third and fourth day. Lethal concentrations to snails were LC50 = 9.6 mg/l (95% CI: 6.3 to 19.4) in one set and LC50 = 6.8 mg/l (95% CI: 5.4 to 12.2) in the other. Adding river water to one set of the experiments had no effect on the mean saponin concentration over time (F = 0.02, P = >0.05). (2) Comparison of the hemolytic assay with the HPLC method showed no significant difference in mean saponin concentrations (t = 0.32, P > 0.05, 95% CI: -2.67 to 3.64), and a correlation of r2 = 0.88 between the two methods. (3) The saponin fraction of an aqueous extract of P. dodecandra was readily biodegraded (t1/2 = 15.8 h), and the complete consumption within a 10-day window indicates ready degradability in aquatic environments under aerobic conditions. (4) These results show that the use of Endod berries for snail control in schistosomiasis-infested water bodies is environmentally acceptable.