As part of a New Zealand-based search for biologically active metabolites from marine organisms, we instigated an investigation into the chemistry of deeper-water (> -40 m) invertebrates. The initial collection in 1983 led ultimately to the isolation of a series of new and known halichondrins, potent antimitotic agents. The second collection, also by benthic dredging, was along the Chatham Rise off the East Coast of South Island of New Zealand in 1995. Cytotoxicity screening of extracts from this collection against the P388 cell line yielded an incidence of activity ~2×-higher (37%) than the average of the previous 13 years of collecting (>5000 shallow-water samples), confirming the potential of both deeper-water invertebrates and the Chatham Rise as a rich source for biologically active organisms. The most potent extracts belonged to a sponge identified as Lamellomorpha strongylata. We report here the isolation of three novel cytotoxic compounds from this organism as well as a surprising result from an examination of the active components from a further organism from the Chatham Rise collection.