A single stress, acidification with sulfuric acid, was applied to Little Rack Lake in a whole-ecosystem manipulation. We documented a wide range of responses to the acidification, including increases in the concentrations of various chemicals, shifts in microbial processes and a major increase in water clarity to UV-B radiation. Each of these changes could in itself be considered as a separate ecosystem stress that is distinct from the intended manipulation. Acidification in Little Rock Lake was accompanied by a number of substantial changes in the occurrence of organisms. A series of detailed investigations indicates that the mechanisms underlying these organismal changes are varied but cannot usually be tied to the direct effects of acidification. Overall, our results demonstrate how multiple stresses can arise from a single agent operating on an ecosystem and suggest that singly operating stresses may actually be quite rare.