A set of aminosubstituted neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives has been synthesized and evaluated for in vitro activity against Schistosoma mansoni adult worms. Six out of 18 derivatives showed significant antischistosomal activity with 100% worm mortality at a concentration of 5 lg/ml after 5 days. The most effective compound is neocryptolepine 10d having IC50 and IC90, 2.70 and 3.95 lM/ml for Egyptian Schistosoma strains, respectively. It is clear from the results that introducing N-substituted side-chains into the indoloquinoline core structure significantly increased the antischistosomicidal activity. The structure–activity relationships of this series of compounds are discussed.