Peptides can have widely varying solubility properties, depending largely on their primary sequence. While many research peptides dissolve easily in water, some, especially those containing multiple hydrophobic amino acid residues, may not readily dissolve. As a general procedure, we recommend first attempting to reconstitute peptides in sterile, distilled water, with sonication if necessary. If solutability is still a problem, addition of a small amount of dilute (approximately 10%) aqueous sterile acetic acid (for basic peptides, PI < 7) or aqueous ammonia (for acidic peptides, PI >7) may facilitate dissolution of the peptide. If solubility issues still persist, it is likely to be a highly hydrophobic peptide, and may require an organic solvent such as Acetonitrie, DMF, or DMSO in order to get the peptide into solution. It may be desirable, initially, to determine solutability on an aliquot of the total sample. The buffer of choice for your experiments should only be added after the peptide is fully in solution, since salts may promote aggregation and therefore create solubility problems.