The use of multi-parametric flow cytometry in high complexity applications has recently made a significant jump in the number of color combinations that can be included in multi-color cocktails. With the technological advancements in new polymer dyes, as well as advances in instrument optical design, fluidics, electronics and software, the need for data driven approaches in panel design are critically needed. Today, we will outline a structured process for designing an 18 multi-color cocktail designed to interrogate both the B cell and T cell compartments in normal blood. Design of the panel will incorporate receptor density data, receptor co-expression information, the sensitivity of each detector using a CD4 stain index, the FMO for each antibody conjugate and the spillover spread matrix across all colors and detectors. Complex comparative expression patterns will be analyzed across 6 normal donors, outlining the complexity of the B and T cell compartments.