Marine biofouling organisms such as blue mussels, barnacles, and macroalgae cause serious problems to ships' hulls, the cooling system of power plants, and fishing nets. Organotin compounds like TBTO have been used as antifouling agents but pose toxic risks to the marine environment, creating a need for less toxic alternatives. A new diterpene-alkaloid, epi-agelasine C, was isolated from the marine sponge Agelas mauritiana using a screening method for antifouling activity against the macroalga Ulva conglobata. Its structure was elucidated by spectral means (HRFABMS, 1H- and 13C-NMR, NOE, HMBC) and identified as a stereoisomer of agelasine C with the molecular formula C26H39N5. Activity tests showed epi-agelasine C had antifouling activity against Ulva spores (though less potent than CuSO4), lethal activity against Ulva fronds at 50 ppm, and antimicroalgal activity against red tide organisms (Oscillatoria amphibia, Skeletonema costatum, Brachiomonas submaria, Prorocentrum micans) at 1.0–2.5 ppm. It did not exhibit antibacterial activity against Staphylococcus aureus, Vibrio costicola, Escherichia coli, or Bacillus subtilis.