Natural-abundance N-15 NMR spectroscopy on dodecylguanidine reveals solvent and protonation effects that model those that could occur for the arginine side chain in proteins. Our results demonstrate that the N-15 chemical shifts of the terminal guanine nitrogens strongly depend on the solvent chosen for measurements. A polar H-bond-donating solvent like water has strongly deshielding effects on the neutral guanidine group (with the latter acting predominantly as an H-bond acceptor). As a result, a substantial upfield shift occurs when neutral guanidine is dissolved instead in a non-H-bonding solvent (chloroform). These solvent effects can be as large as those induced by protonation changes. This limits the ability of N-15 chemical shifts to distinguish the protonation state of the arginine side chain, at least without specific knowledge of its environment. These results help to reconcile previous interpretations about the protonation state arg-82 in the M state of bacteriorhodopsin based on FrIR and N-15 NMR spectroscopy. That is, contrary to earlier conclusions from solid-state NMR, the side chain of arg-82 could undergo a deprotonation between the bR and M states, but only if it also experienced a significant decrease in the H-bonding character and polarity of its environment. In fact, the average N-15 chemical shift of the two N-eta of arg-82 in bacteriorhodopsin ' s M intermediate (from the previous NMR measurements) is 17 ppm upfield from the corresponding value for the deprotonated arginine side chain in aqueous solution at pH > 14, but only 3 ppm upfield from the value for deprotonated dodecylguanidine in chloroform.