Cellular differentiation can be observed in certain filamentous blue-green algae after transfer of the cells from medium containing NH(4) (+) or NO(3) (-) to nitrogen-free medium. The appearance of differentiated cells (heterocysts) is accompanied by an increase in the activity of nitrogenase, an enzyme complex that reduces N(2) to NH(3). We have separated vegetative cells from heterocysts in differentiated filaments of Nostoc muscorum, and analyzed their proteins by polyacrylamide-gel electrophoresis. The pattern of incorporation of (35)SO(4) (-) into proteins of the two cell types during differentiation indicates that the increase in nitrogenase activity is due to the de novo synthesis of nitrogenase proteins predominantly, if not exclusively, in heterocysts.