In vitro and in vivo studies were conducted to assess the response of chole
ra toxin (CT) production to increasing iron concentrations in an aquatic en
vironment. Production of CT by seven of eight Vibrio cholerae strains teste
d, including the Bengal strain (O139), was significantly enhanced in the pr
esence of iron concentrations of 1.0 and 10 g/L. The exception (El Tor Ogaw
a) had a significant CT response only in the presence of 10 g of iron/L. En
hancement of CT production also occurred at iron concentrations less than 1
.0 g/L, but not to a statistically significant degree. The high iron concen
trations, which in this study were found to stimulate CT production, have b
een described by others in association with sediments, water plants, and ch
itinous fauna. Other investigators have shown a predilection by V. choler-n
e to attach to these sites in the aquatic environment. The importance of ex
cess in vivo iron with respect to the pathogenicity of several gram-negativ
e bacilli is well recognized. However, the possible impact of environmental
iron on the in vitro toxigenicity of a microorganism, in this case V. chol
erae in its aquatic environment, is to the best of our knowledge a new find
ing with important epidemiologic implications. These findings, coupled with
the fact that iron concentration is considerably enhanced in industrially
polluted waters and sediments, may reflect a causal link between the concur
rent global upsurge of industrialization and pandemic occurrence of cholera
during the latter half of the 20th century. Enhanced toxigenicity may also
cause clinical disease following ingestion of lower than usual infective d
oses of cholera vibrios, thereby increasing the incidence of symptomatic ca
ses and, possibly, of severe cases.