HMG-1, -2, and -E are a set of sequence homologs from the family of high molecular weight high mobility group nonhistone chromatin (NHC) proteins. 1 A number of interesting observations have been made on the DNA-binding properties of these proteins. We reported that the proteins from several sources possess a preferential affinity for single-stranded DNA. 2 , 3 That conclusion was drawn from chromatography of the proteins on double- and single-stranded DNAs immobilized on cellulose. Javaherian et al. 4 reported that calf thymus HMG-1 and -2 are capable of changing the helical structure of DNA — specifically, of reducing the linking number of nicked circular DNA that is covalently closed in the presence of one of the proteins. That effect could be produced by any of several mechanisms, including unwinding due to preferential binding to single-stranded DNA. 4 Javaherian et al. 5 later reported that calf thymus HMG-1 and -2 were capable of lowering the Tm of poly(dA-dT). Duguet and de Recondo and their colleagues have been studying a single-stranded DNA-binding protein (called S25) from rat liver and a protein (called HD25, indistinguishable in most respects from S25) from regenerating rat liver. Recently that group has identified S25 and HD25 as cytosolic forms of rat HMG-1. 6 HD25 (hence, cytosolic HMG-1 from regenerating rat liver) has been reported to be capable of lowering the Tm of poly(dA-dT). 7 , 8