The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.