The cyanobacterium Synechocystis sp. strain PCC 6308 has been shown to exhibit predictable physiological responses to acid stress. Originally isolated from a Wisconsin lake, this cyanobacterium grows optimally under alkaline conditions in the laboratory. After acid stress at a pH of between 4.4 and 7.7, cells return to exponential growth following a lag phase. The organism's response to this tolerable acid stress involves cell concentration-dependent neutralization of the external medium to pH 6 or above within 5 min, maintenance of a transmembrane pH gradient, and maintenance of photosystem II efficiency. Lethal acid stress, at a pH below 4.4, results in the formation of aggregates of denatured proteins observed as granules near the cell periphery, the disruption of the transmembrane pH gradient, cell color change to blue, and damage to photosystem II.