The isolation and characterization of the products formed during the irreversible thermal denaturation of enzyme RNAase-A are described. RNAase-A, when maintained in aqueous solution at pH 7.0 and 70 degrees for 2 h, gives soluble products which have been fractionated by gel filtration on Sephadex G-75 into four components. These components are designated RNAase-At1, RNAase-At2, RNAase-At3 and RNAase-At4 according to the order of their elution from Sephadex G-75. RNAase-At4 shows the same specific activity towards yeast RNA as native RNAase-A and is virtually indistinguishable from it by the physical methods employed. However, chromatography on CM-cellulose separates it into three components that show the same u.v. spectra and specific activity towards yeast RNA as native RNAase-A. RNAase-At1, RNAase-At2 and RNAase-At3 are all structurally altered derivatives of RNAase-A and they exhibit low specific activity (5-10%) towards yeast RNA. In the presence of added S-protein, all these derivatives show greatly enhanced enzymic activity. RNAase-At1 and RNAase-At2 are polymers, covalently crosslinked by intermolecular disulfide bridges; whereas RNAase-At3 is a monomer. Physical studies such as 1H-n.m.r., sedimentation analysis, u.v. absorption spectra and CD spectra reveal that RNAase-At3 is a unfolded derivative of RNAase-A. However, it is seen to possess sufficient residual structure which gives rise to a low but easily detectable enzymic activity.