A series of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carboline derivatives have been synthesized and evaluated for antitumor activity against murine P-388 and human tumor cell lines, KB-16, A-549 and HT-29. All of the compounds prepared, except for 19, showed significant cytotoxicity. Among them, compound 29 exhibited the most potent activity against all tested tumor cell lines. There was an apparent lack of correlation regarding cytotoxicity between 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carbolines. This study is the first to discover compound 29 as a potential lead for the development of future anticancer agents. The mode of inhibition for compound 29 was proposed.