Under the influence of dilute NaCl solutions at 38 °C, collagen fibrils experience a two-dimensional, inner-crystalline swelling, probably as a result of the shielding of the charges of the functional groups. Exposure of collagen to polyvalent ions (Ca2®, Sr2®, and La3) in concentrations higher than 0,4-molar leads to identical alterations of the collagen regardless of the concentration. The fibrils dissociate into longitudinal units of about 80 A diameter. Water can enter the interspaces. The crosslinking of protofibrils into 80 A units could be the result of Ca2⊕ or Sr2⊕ exchange in equimolar amounts. Under the influence of dodecylammonium collagen fibrils swell intensely probably as result of blocking of carboxyl groups. Exposure to other macro-cations present in the body also lead to swelling. All observations agree well with classical ideas of inner-crystalline swelling. The possible biological significance of the phenomena reported is discussed.