The ability to determine the primary structure of a polypeptide was a major advance in biochemistry and sequencing work since then has let to a greater understanding of protein structure and function. At present, protein sequence analysis is at the forefront of modern molecular biology. Partial sequence determinations using microgramme amounts of protein has enabled many genes with low levels of transcription to be cloned and their complete primary structures to be determined. This approach is also the only means available for determining the sites of post-translational modification. This is a laboratory manual aimed at those wishing to isolate proteins or peptides and to carry out subsequent sequence analysis and interpretations of structural significance. It is written for both professional and inexperienced research workers and for those with and without access to high technology instrumentation. The protocols used have been selected for their general utility.