<jats:title>Abstract</jats:title><jats:p>Investigation of the most polar fractions obtained from the organic extract of the Caribbean marine sponge <jats:italic>Plakortis simplex</jats:italic> has led to the isolation of three novel iodine‐containing tryptophan betaines structurally related to the known hypaphorine (<jats:bold>5</jats:bold>), which have been named plakohypaphorine A (<jats:bold>2</jats:bold>), B (<jats:bold>3</jats:bold>) and C (<jats:bold>4</jats:bold>). Their structures have been determined by spectroscopic methods. Isolation of compounds <jats:bold>2−4</jats:bold> is particularly remarkable since it represents the first finding of iodoindole derivatives in a natural source, either marine or terrestrial. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)