Recent reviews document that hyperthermic shock inhibits the major nuclear activities, including semiconservative DNA replication (1, 2). These inhibitions may result either from a direct effect of heat on the cell nucleus or as a consequence of changes in other cell compartments [e.g., cell membrane damage (3)]. Here we review recent results concerning heat-induced changes in mammalian cell nuclear structure and function, principally DNA replication. These data are discussed in terms of a current model of nuclear organization in order to relate these heat-induced alterations in the nucleus to known cellular effects of heat, such as cytotoxicity and alterations in DNA synthesis.