On Guam, the nudibranch Glossodoris pallida specializes in feeding on the branching sponge Cacospongia sp., which contains scalaradial and desacetylscalaradial as major secondary metabolites. The nudibranch, which accumulates both compounds for its own defense, is typically found on the base of the sponge. In this study, we quantified intracolonial variation in the production of secondary metabolites (percent yield of crude extract, filtered extract, scalaradial, and desacetylscalaradial), structural material (fiber and ash content), and protein content in Cacospongia sp. in order to assess the consequences that such variation has on feeding responses of generalist fish predators, the specialist nudibranch predator G. pallida, and on the distribution of the nudibranch on the sponge. Levels of secondary metabolites varied among the parts of the sponge analyzed (tip, base, surface, and matrix). The mean peicer,: y-ic!d of cr. ; dc cx!:zct :vs: $isher i?, the surface nf !he spc~cje. .uhi!e filtered extract and desacetylscalaradial were higher in tips than in bases Structural materials were highest in the base and in the surface of the sponge. In contrast, the inner part of the sponge contained higher levels of protein than the surface, but no differences were found between tips and bases. Compared to a control, the crude extract of Cacospongia sp. significantly deterred fish feeding at the lowest concentration found in the sponge (base concentration) In field assays. When offered a cholce between base and t~p concentrations, both the pufferfish Callthiyaster solandn in laboratory assays and the natural reef fish assemblage in the field showed no preference for extracts of bases over tips (i.e. lower levels over higher levels of chemical defenses). However, when offered a choice between pieces of sponge from the base and from the tip, the nudibranch G. pallida preferred bases over tips, which agrees with the nudibranch distribution on the sponge. Alternative factors may shape the observed distribut~on of nudibranchs on Cacospongia sp. Nudibranchs at the bases may suffer lower levels of predation because they are less accessible to predators than nudibranchs at the tips of the sponge Therefore, we also tested whether small disks of artificial squid food located on tips and bases of the sponge are equally accessible to generalist fish predators. The reef fish C. solandri in laboratory assays and the natural fish assemblage at the Cacospongia sp. community consumed equal amounts of food from tips and bases. Our data demonstrate that Cacospongia sp. extracts deter feeding by fishes at the lowest concentration found in the sponge, which suggests that the higher concentration in the tips is not a mechanism to avoid consumption by generalist fish predators. In contrast, avoidance of higher levels of chemistry appears to be the factor behind the selection of bases over tips by the specialist nudibranch predator G. pallida. Intracolonial variation in chemical defenses seems to determine the nudibranch distribution o...