The relationship of polyamine accumulation and semiconservative DNA replication was studied in synchronous Chinese hamster ovary cultures, progressing through the cell cycle normally at 37.degree. C or after hyperthermic exposure (43.degree. C for 1 h) during G1 or S phase. In control cultures, intracellular polyamine levels decreased as cells divided and then reaccumulated as cells existed G1 and proceeded through the S and G2 phases. Immediately after cultures were exposed to 43.degree. heat for 1 h in G1 phase, intracellular levels of spermidine and spermine were reduced compared to controls. Coordinate with the depletion of the intracellular levels of these polyamines following exposure at 43.degree. C, extracellular levels of spermidine and spermine were increased. The ratio of intracellular to extracellular amounts of these polyamines changed from 1-1.5 to .apprx. 0.2-0.3 after hyperthermic exposure. These cultures exposed to 43.degree. C heat during G1 initially showed depressed levels of replicated DNA, but near-control rates of DNA replication were attained in a temporally related manner with the reaccumulation of intracellular spermidine and spermine levels. When cultures were exposed to 43.degree. C heat in S phase, intracellular amounts of spermidine and spermine were again reduced, and increased extracellular levels of these polyamines were observed. In these S phase treated cultures, cells were able to continue replicating their DNA but at a reduced rate compared to controls. These results and others show that exposure of cells at 43.degree. C causes a depletion of intracellular levels of spermidine and spermine, suggesting that an immediate aspect of thermal damage is a membrane defect that affects the transport of these molecules across cell membranes. Exposure of G1- or S phase cultures to 43.degree. C heat caused a depression of bulk DNA synthetic rates resulting in a prolongation of the S phase. The intracellular reaccumulation of spermidine and spermine following exposure of G1 cells to a 43.degree. C heat shock is temporally related to the recovery of near-normal DNA synthetic rates in these cells. [This study is a model for cancer treatment by hyperthermia.].