The accumulation of high levels of low-molecular-weight solutes (polyhydric alcohols, saccharides) provides cryoprotection to freeze-tolerant animals by minimizing, via colligative effects, the percentage of body water converted to extracellular ice and the extent of cell volume reduction. Many freeze-tolerant insects accumulate high levels of polyols during autumn cold hardening, whereas freeze-tolerant frogs respond to ice formation in peripheral tissues by synthesizing large amounts of glucose in the liver and rapidly distributing the sugar throughout the body. Seasonal patterns of enzymatic change occur in cold-hardy insects; activities associated with cryoprotectant synthesis rise in the fall, whereas enzymes associated with polyol degradation dominate in the spring. Enzyme profiles also revealed the route of glycerol degradation via polyol dehydrogenase and the novel enzyme, glyceraldehyde kinase. Proton magnetic resonance imaging of freezing and thawing in whole frogs showed a new adaptive effect of the very high glucose levels in core organs; during thawing, organs such as liver and heart melted first, allowing recovery of their vital functions to begin while the rest of the frog thawed. New studies have examined signal transduction in the stimulation of glucose production by wood frog liver, revealing the key role of beta-adrenergic receptors and cAMP-mediated activation of glycogenolysis for cryoprotectant synthesis. The seasonal elevation of plasma membrane glucose transporters was also shown to be key to cryoprotectant distribution during freezing. Other new work has shown that frog freeze tolerance probably grew out of preexisting mechanisms of amphibian dehydration tolerance and that both freeze-tolerant and -intolerant frogs show a hyperglycemic response to desiccation at 5 degrees C.