To investigate the conformation-activity relationship, new indolactam derivatives with a fluorine atom at position 5 or 6 were synthesized. (-)-5-Fluoroindolactam-V (2) existing mainly as the sofa conformer in solution was far less biologically active than (-)-6-fluoroindolactam-V (3) existing mainly as the twist conformer. This suggests that the sofa conformation of (-)-indolactam-V (1) is not a biologically active form. Teleocidins (for example, teleocidin A-l and teleocidin B-4) are potent skin tumor promoters produced by actinomycetes. Teleocidins and their core structure (-)-indolactam-V (1) exist as two stable conformers, a twist and a sofa form, in solution at room temperature. Although recent structure-activity studies using a number of indolactam derivatives have revealed the essential structural factors for tumor-promoting activity, the active conformation of teleocidins remains unclear. To solve this problem, conformationally restricted analogues of teleocidins are indispensable. We have previously reported that 5-substituted indolactam derivatives such as (-)-5-acetyl- and (-)-5-chloroindolactam-V exist exclusively as the sofa conformer. However, the biological activities of these derivatives are expected to reflect both the conformational change and the steric effect at position 5 of the indole ring. To estimate more exactly the activity of the sofa conformer, it is necessary to minimize the steric, electronic, and hydrophobic effects of the substituent at position 5. The most promising candidate is (-)-5-fluoroindolactam-V (2). This communication describes the synthesis and biological activities of (-)-5-fluoroindolactam-V (2) along with those of (-)-6-fluoroindolactam-V (3) as a positive control.