Cardiac cells treated with a cryoprotectant can survive freezing to liquid nitrogen temperatures. By currently used techniques, however, whole mammalian mature hearts have survived freezing at temperatures no lower than -20°C. Ultramicroscopic evidence obtained from mammalian liver and smooth muscle cells indicates that their incubation in a balanced salt solution is not entirely innocuous. The freezing of skeletal muscle without the benefit of a cryoprotectant results in a biochemical derangement known as thawrigor, which is sometimes obvious on even the physiological and histological levels. A comparable phenomenon may occur in cardiac muscle. The treatment of cells with a cryoprotectant can cause mild ultrastructural alterations. This may be partly due to osmotic effects of the agent. In cardiac muscle, cryoprotectants in effective doses cause a reversible cessation of contraction known as a pseudotoxic effect. A true toxic effect, irreversible cessation of contractions, is manifested when the cryoprotectant is in excessive concentration or is incubated with the tissue for prolonged periods of time. The decreased toxicity seen when the agent is administered as a cold solution may be a result of decreased diffusion rates with a concomitant decreased tissue or cellular concentration. When a cryoprotectant is administered by vascular perfusion to a whole organ, the osmotic effect is to withdraw water from the cellular and interstitial compartments. When an organ which has been equilibrated with 2.1 m glycerol or DMSO is perfused with a balanced salt solution (plus colloid), the extravascular compartment swells and produces vascular insufficiency and even occlusion. © 1969.