It is not clear what the upper temperature limit for life is, or what speci
fic factors will set this limit, but it is generally assumed that the limit
will be dictated by molecular instability. In this review, we examine the
thermal stability of two key groups of biological molecules: the intracellu
lar small molecules/metabolites and the major classes of macromolecules. Ce
rtain small molecules/metabolites are unstable in vitro at the growth tempe
ratures of the hyperthermophiles in which they are found. This instability
appears to be dealt with in vivo by a range of mechanisms including rapid t
urnover, metabolic channelling and local stabilisation. Evidence to date su
ggests that proteins have the potential to be stable at substantially highe
r temperatures than those known to support life, but evidence concerning de
gradative reactions above 100 degrees C is slight. DNA duplex stability is
apparently achieved at high temperature by elevated salt concentrations, po
lyamines, cationic proteins, and supercoiling rather than manipulation of C
-G ratios. RNA stability seems dependent upon covalent modification, althou
gh secondary structure is probably also critical. The diether-linked lipids
, which make up the monolayer membrane of most organisms growing above 85 d
egrees C are chemically very stable and seem potentially capable of maintai
ning membrane integrity at much higher temperatures. However, the in vivo i
mplications of the in vitro instability of biomolecules are difficult to as
sess, and in vivo data are rare.