Sequences of 40 very diverse representatives of the alpha-crystallin-small heat-shock protein (alpha-Hsp) superfamily are compared. Their characteristic C-terminal 'alpha-crystallin domain' of 80-100 residues contains short consensus sequences that are highly conserved from prokaryotes to eukaryotes. There are, in addition, some positions that clearly distinguish animal from non-animal alpha-Hsps. The alpha-crystallin domain is predicted to consist of two hydrophobic beta-sheet motifs, separated by a hydrophilic region which is variable in length. Combination of a conserved alpha-crystallin domain with a variable N-terminal domain and C-terminal extension probably modulates the properties of the various alpha-Hsps as stress-protective and structural oligomeric proteins. Phylogeny reconstruction indicates that multiple alpha-Hsps were already present in the last common ancestor of pro- and eukaryotes. It is suggested that during eukaryote evolution, animal and non-animal alpha-Hsps originated from different ancestral gene copies. Repeated gene duplications gave rise to the multiple alpha-Hsps present in most organisms.