Addition of trivalent lanthanide salts to solutions of hyaluronan (HA), a naturally occurring anionic polysaccharide, resulted in an unexpected reverse-temperature phase transition (RTPT); i.e., the complexes were soluble when cooled but precipitated when warmed. A unique lower critical solution transition temperature (LCST) was observed for each lanthanide in the order (increasing LCST) Eu3+ < Nd3+ < Ce3+ < Gd3+ < La3+ < Tb3+ < Dy3+ < Yb3+ < Lu3+ for high molecular weight HA. Moreover, the LCST values increased as the molecular weight of the HA decreased from 1730 to 190 kDa. The precipitation-dissolution behavior was fully reversible in a cyclical fashion; a lag in redissolution was observed as the temperature was lowered. and longer incubation times at each temperature minimized this lag. The RTPT behavior could be ablated by titration with 8 kDa HA to produce complexes soluble at ambient temperature. This is the first description of RTPT behavior in a biologically important glycosaminoglycan.