From the late 1950s to the mid-1970s, American experimental musicians like Pauline Oliveros, David Tudor, and Gordon Mumma employed complex and idiosyncratic technological systems to produce and capture acoustic resonance for aesthetic appreciation. Although this shared exploration exhibited many of the hallmarks of a genuine research project, scholars of experimental music have long been wary of claims that there is anything particularly scientific about this music, frequently comparing its informality unfavorably with the rigor and empiricism of the individual scientific experiment. However, historian of science Hans-Jörg Rheinberger has long held that the fundamental working unit of scientific research is not the individual experiment, but what he terms the experimental system: The loose coherence of objects, instruments, and technologies through which research questions are materialized over time. I argue that Rheinberger's framework of the experimental system offers a compelling way of understanding the experimentation that catalyzed the emergence of what has come to be known as “resonance aesthetics” in American experimental music. By focusing on the material links of musicians’ activities, the experimental system illuminates how knowledge was produced and circulated within and between vastly different musical performances. Rheinberger's characterization of successful research also informs a more nuanced conception of virtuosity in experimental music. Finally, this framework is an opportunity to re-evaluate the status of sound as an object of epistemological inquiry, akin to what Rheinberger describes as an “epistemic thing.” In theorizing epistemic sound as both contextual and emergent, I re-evaluate musicians’ approaches to spontaneity and improvisation in musical performance.