Hydrophobic interactions mediated by nonpolar molecular fragments in water are influenced by local chemical and physical contexts in ways that are not yet fully understood. Here, we use globally amphiphilic (GA) beta-peptides (GA-Lys and GA-Arg) with stable conformations to explore if replacement of beta(3)-homolysine (beta Lys) with beta(3)-homoarginine (beta Arg) influences the hydrophobically driven assembly of these peptides in bulk aqueous solution. The studies were conducted in 10 mM triethanolamine buffer at pH 7, where both beta Lys (ammonium) and beta Arg (guanidinium) side chains are substantially protonated. Comparisons of light scattering measurements and cryo-electron micrographs before and after the addition of 60 vol% MeOH indicate very different outcomes of the hydrophobically driven assembly of AcY-GA-Lys versus AcY-GA-Arg (AcY denotes an N-acetylated-beta(3)-homotyrosine (beta Tyr) at each N-terminus). Nuclear magnetic resonance and analytical ultracentrifugation confirm that AcY-GA-Lys assembles into large aggregates in aqueous buffer, whereas AcY-GA-Arg at comparable concentrations forms only small oligomers. Titration of AcY-GA-Arg into aqueous solutions of AcY-GA-Lys reveals that the driving force for AcY-GA-Lys association is far stronger than that for AcY-GA-Arg association. We discuss these results in the light of past experimental observations involving single molecule force measurements with GA beta-peptides and hydrophobically driven dimerization of conventional peptides that form a GA alpha-helix upon dimerization (but do not display the Lys versus Arg trend predicted by extrapolating from the earlier AFM studies with beta-peptides). Overall, our results establish that the identity of proximal cationic groups, ammonium versus guanidinium, profoundly modulates the hydrophobically driven self-assembly of conformationally stable beta-peptides in bulk aqueous solution.