Purines and pyrimidines play a key role in nucleic acid and nucleotide meta
bolism of all cells. In addition, they can be used as nitrogen sources in p
lants and many microorganisms. Transport of nucleobases across biological m
embranes is mediated by specific transmembrane transport proteins. Nucleoba
se transporters have been identified genetically and/or physiologically in
bacteria, fungi, protozoa, algae, plants and mammals. A limited number of b
acterial and fungal transporter genes have been cloned and analysed in grea
t detail at the molecular level. Very recently, nucleobase transporters hav
e been identified in plants. In other systems, with less accessible genetic
s, such as vertebrates and protozoa, no nucleobase transporter genes have b
een identified, and the transporters have been characterized and classified
by physiological and biochemical approaches instead. In this review, it is
shown that nucleobase transporters and similar sequences of unknown functi
on present in databases constitute three basic families, which will be desi
gnated NAT, PRT and PUP. The first includes members from archea, eubacteria
, fungi, plants and metazoa, the second is restricted to prokaryotes and fu
ngi, and the last one is only found in plants. Interestingly, mammalian asc
orbate transporters are homologous to NAT sequences. The function of differ
ent nucleobase transporters is also described, as is how their expression i
s regulated and what is currently known about their structure-function rela
tionships. Common features emerging from these studies are expected to prov
e critical in understanding what governs nucleobase transporter specificity
and in selecting proper model microbial systems for cloning and studying p
lant, protozoan and mammalian nucleobase transporters of agricultural, phar
macological and medical importance.