A number of facts relating to proteins suggest that the polypeptides in native protein are in a folded state (Astbury 1933, 1934; Astbury and Street 1930, 1931; Pryde 1931; Wrinch 1936
a
,
b
,
c
, 1937
a
; Langmuir, Schaefer and Wrinch 1937). The type of folding must be such as to imply the possibility of the regular and orderly arrangement of hundreds 01 amino-acid residues which to some extent at least is independent of the particular residues in question. We propose therefore to formulate all types of folding which are geometrically possible. Each hypothesis in turn can then be tested in two ways. We may consider its plausibility in itself: and having developed its implications to the farthest possible point, we may test it against known facts by
ad hoc
experiments. At present two types of folding have been suggested—by means of cyclol links (Wrinch 1936
a
,
b
,
c
, 1937
a
; Langmuir, Schaefer and Wrinch 1937; Astbury 1936
a
,
b
,
c
; Frank, 1936) and by means of hydrogen bonds (Jordan Lloyd 1932; Jordan Lloyd and Marriott 1933; Mirsky and Pauling 1936; Wrinch and Jordan Lloyd 1936). The search for other types of folding is being continued. So far it has not proved possible to discard either theory on the grounds that the type of link postulated is out of the question. It is there fore very desirable to test these theories by means of their implications. Accordingly, on this occasion we consider (Wrinch 1937
b
,
c
) whether the cyclol theory can stand the test of the body of facts relating to the “globular” proteins, established by Svedberg and his collaborators (Svedberg and others 1929, 1930
a
,
b
, 1934
a
,
b
, 1935).
The cyclol hypothesis and the “globular” proteins