It is difficult to clearly and unambiguously demonstrate an allelopathic mechanism of plant interference. Several types of experimental methodologies such as the additive design, substitutive designs, and several types of plant yield-plant population functions are discussed in terms of their relative merits in terms of providing quantitative and qualitative information in the development of an empirical basis to describe a plant interaction. Additionally, several types of mathematical and graphical representations are presented using data from the velvetleaf (Abutilon theophrasti) and soybean (Glycine max) interaction. The design provides agronomically relevant information about crop yield losses but confounds the separate effects of population density and species proportion in mixtures. The replacement series design separates these two variables by maintaining a constant population of plants while varying the relative proportion of each species in mixtures. The replacement series diagram, relative yield, relative replacement rate, ratio diagram, a scaling test, and the regression of individual yield on the associate yield are discussed in terms of their utility in providing insights into a plant interaction. Individual plant yield-plant population functions such as the “Y-D” and “C-D” effects, the “3/2 power law of self-thinning,” and the “Sakai” test provide a basis to compare plant yield per plant versus plant population responses. Several types of interactions are characterized with this methodology. None of these experimental designs will clearly demonstrate an allelopathic plant interaction alone, but they do provide high-inference experimental methodologies to develop an empirical foundation to describe accurately a plant interaction upon which more specific hypotheses can be developed.