Increasing evidence is accumulating that the origin of genetic regulation of many microbial secondary metabolites can be traced to inter-kingdom and inter-generic interactions within the native ecosystem of producing organisms. We ask the question: if secondary metabolites are generally produced in response to external biochemical and biological stimuli, can they be stimulated and revealed within a metabolome by analyzing and organizing trends in the metabolite intensities across panels of stimuli for a single organism grown in a single medium? Here we provide data in support of the hypothesis that secondary metabolites are mediators of stimuli response and we describe a system to organize the metabolomic responses into maps that specifically reveal secondary metabolites. First, in a model genomically characterized Streptomyces, we demonstrate how a significant fraction of known secondary metabolism is stimulated and displayed via stimulus mapping and how a large fraction of transcriptionally silent metabolism can be activated and identified without genetic recombinant manipulation. Second, we apply this method to the discovery of several new polyketides, including a highly modified aromatic and a new macrolactam, from a genomically characterized Nocardopsis species.