Steroids isolated from marine sponges frequently contain substantially modified side chains. The most commonly encountered modifications involve extensive alkylation and/or dealkylation. Recently, a small group of biologically active steroids containing more complex side chain functional groups have been reported from sponges. Examples include the following: a family of sterol disulfates that contain a side-chain orthoester; the xestobergsterols, which have a C16/C23 bond that generates a new cyclopentane ring involving side-chain and ring D carbon atoms; contignasterol, which contains a cyclic hemiacetal in the side chain; and the kiheisterones, which contain a C21 carboxylic acid and a furan ring in the side chain. As part of an ongoing investigation of the secondary metabolites of cold water marine invertebrates, it was found that extracts of the Norwegian sponge Polymastia boletiformis (Lamarck, 1815) exhibited antimicrobial activity. Bioassay guided fractionation of the P. boletiformis extracts led to the isolation of the pure antimicrobial metabolite polymastiamide A (1) and a complex mixture of minor analogs. The interesting side chain modification in polymastiamide A (1), which involves linkage to a nonprotein amino acid via an amide bond, is to the best of our knowledge without literature precedent.