Bioassay-guided fractionation of organic extracts from two Lyngbya majuscula collections led to the isolation of a new secondary metabolite, antillatoxin B, an unusual N-methyl homophenylalanine analogue of the potent neurotoxin antillatoxin. Its structure was deduced from 2D NMR and data comparisons with antillatoxin. Antillatoxin B exhibited significant sodium channel-activating (EC(50) = 1.77 microM) and ichthyotoxic (LC(50) = 1 microM) properties.