Nitrosothiols are powerful vasodilators. Although the mechanism of their formation near neutral pH is an area of intense research, neither the energetics nor the kinetics of this reaction or of subsequent reactions have been addressed. The following considerations may help to guide experiments. (1) The standard Gibbs energy for the homolysis reaction RSNO -> RS center dot + NO center dot(aq) is +110 +/- 5 kJ mol(-1). (2) The electrode potential of the RSNO, H+/RSH, NO center dot(aq) couple is -0.20 +/- 0.06 V at pH 7. (3) Thiol nitrosation by NO2- is favorable by 37 +/- 5 kJ mol(-1) at pH 7. (4) N2O3 is not involved in in vivo nitrosation mechanisms for thermodynamic - its formation from NO2- costs 59 kJ mol(-1) - or kinetic - the reaction being second-order in NO2- - reasons. (5) Hemoglobin (Hb) cannot catalyze formation of N2O3, be it via the intermediacy of the reaction of Hb[FeNO2](2+) with NO center dot (+81 kJ mol(-1)) or reaction of Hb[FeNO](3+) with NO2- (+88 kJ mol(-1)). (6) Energetically and kinetically viable are nitrosations that involve HNO2 or NO center dot in the presence of an electron acceptor with an electrode potential higher than -0.20 V. These considerations are derived from existing thermochemical and kinetics data.