We report the testing of 135 non-toxic phosphodiesterase inhibitors developed at Vrije Universiteit Amsterdam (VUA), University of Antwerp (UA) and CSIC, with molecular weights between 234 and 606, for their potential antischistosomal activity. The compounds were assessed for killing of adult mature and early mature Schistosoma mansoni worms in vitro; female ovipositing capacity and worm coupling. Findings of one or two repeat experiments revealed potential antischistosomal activities against adult mature schistosomes, expressed as worm killing/ and or sluggish worm movement or exaggerated spastic worm contractions for 25 compounds. However, the effect was recorded at high concentrations of 100 μM and 50 μM, resulting in worm killing of 20%-100% and 27%-50% respectively for 56% of the compounds (14) with the survivors showing sluggish movement. Sluggish worm movement without killing was recorded for five of the compounds (20%) with absence of ova for two compounds. 24% of the compounds (six) revealed exaggerated spastic worm contractions. In 24 out of 25 promising compounds, only male worms were affected and 100% of those were killed. Meanwhile insult to early mature worms was more pronounced. The percentage worm killing recorded at 25 μM of test compounds was 0%-44%, with the insult still directed against male worms only.