The isolation and structure elucidation of belamide A from the marine cyanobacterium Symploca sp. is described. Belamide A is a highly methylated linear tetrapeptide with structural analogy to the important linear peptides dolastatins 10 and 15. Disruption of the microtubule network in A-10 cells was observed at 20 lM and displayed classic tubulin destabilizing antimitotic characteristics. The moderate cytotoxicity of belamide A (IC50 0.74 lM vs HCT-116 colon cancer line) provides new insights into structure–activity relationships for this drug class.