A system for the regulation of gene expression by ambient (extracellular) pH was first identified in Aspergillus nidulans. This system consists of the products of the pacC and palA, B, C, F, H, and I genes. pacC encodes a zinc finger transcription factor and these pal genes encode components of an ambient pH signal transduction pathway. pH regulatory systems have also been identified in other fungi. Components of these regulatory systems are homologous to those in A. nidulans. This review describes the pH regulatory system in A. nidulans and the history of this research and how it relates to other systems. pH regulation in bacteria and animal cells is also briefly discussed.