The effects of vitamin B-12 availability on the physiology of the cyanobacterium Synechococcus sp. strain PCC 7002 were examined in a continuous culture chemostat system. The availability of vitamin B-12 within the system was demonstrated to control the cell density and cellular chlorophyll levels under nutrient-limiting conditions. Electron micrographs of vitamin B-12 replete and vitamin B-12 deficient cyanobacteria indicated that a reduction in vitamin B-12 availability induced a loss of thylakoid integrity within the system. Polyacrylamide gel electrophoresis demonstrated that the expression of outer membrane proteins of 95, 70, and 34 kDa was enhanced during vitamin B-12 limited growth. Cellular quotients were determined to be a minimum of 256 molecules of vitamin B-12/cell to sustain a growth rate of 0.6/day. A comparison with eukaryotic plankton demonstrated that the vitamin B-12 requirements of cyanobacteria may be more similar to those of chloroplasts than to those of the entire group of eukaryotic algae.