The possible existence of genetically distinct populations of spawning striped bass (Morone saxatilis) in the river systems of the upper Chesapeake Bay was investigated by a biochemical genetic approach. Samples of blood and liver from adult fish were obtained during the 1976 spawning runs from the Rappahannock (Virginia), Potomac, Choptank, Sassafras, Bohemia, and Elk rivers (Maryland), and Maryland waters of the Chesapeake and Delaware Canal. Samples were analyzed for frequency of occurrence of a polymorphic liver enzyme, glycerol-3-phosphate dehydrogenase, and variable serum proteins which were not correlated with age or sex. Multivariate and Bayesian analyses of these data indicate apparent genetic homogeneity of spawning bass within the upper Chesapeake Bay. If natal stream homing occurs, a sufficient number of wanderers may provide significant gene flow among river systems. The results suggest that long-term management of the fishery need not be totally on the basis of separate river units.