A new cytotoxic macrocyclic diterpenoid, euphornin L (1), together with seven known analogues were isolated from the plant Euphorbia helioscopia L. The structure of 1 was elucidated by spectral data and X-ray crystallographic analysis. Euphornin L (1) and euphoscopin F (2) exhibited significant cytotoxicity against HL-60 cell lines with IC(50) values of 2.7 and 9.0 microM, respectively. The 13C-NMR data of euphoscopin F (2), epieuphoscopin B (3), euphoscopin B (5), and euphoscopin C (6) were also reported for the first time.