Multistep organic solvent-based pharmaceutical syntheses of larger organic microsolutes having molecular weights (MW) in the range of 300-1000 generally require athermal separation processes because the active molecules and the intermediates are thermally labile. To that end, nanofiltration (NF) of methanol solutions of three selected solutes, safranin O (MW 351), brilliant blue R (MW 826) and vitamin B-12 (MW 1355) has been studied in a batch stirred cell for a dilute solution of each individual solute at 3034 kPa (440 psig). The solvent-resistant membranes investigated and their manufacturer-specified molecular weight cut-offs (MWCO) are MPF-44 (250), MPF-50 (700) and MPF-60 (400). During an initial transient period, the solvent flux decreased with time and the solute rejection increased with time for every membrane reaching a steady state after about 12 h. This behavior resulting from membrane compaction and pore size reduction was partially reversible. Additional studies using higher feed solute concentrations (1 and 3 wt.%) show considerable reduction in solvent flux and increase in solute rejection; the effect appears to be far more than that due to an increase in osmotic pressure and possible reasons for such a behavior have been suggested. The observed solute rejection values are generally significantly lower than the manufacturer-specified MWCO values. Additional studies varying the feed solution pressure through the membrane MPF-60 indicate that the variation of the percent rejection of solutes safranin O and brilliant blue R with the solvent flux tends to follow the relation suggested by the Finely Porous Model.