Macrophage aggregate (MA) abundance in fish is a useful general biomarker of contaminant exposures and environmental stress. Hepatic and splenic MAs were evaluated in semi-anadromous white perch Morone americana (Gmelin, 1789) from the urbanized Severn River (S) and the more rural Choptank River (C), Chesapeake Bay. Fish were collected from different sites in the annual migratory circuit in each river that corresponded to active spawning in late winter-early spring, summer regenerating, autumn developing, and winter spawning-capable phases. An age-associated progressive increase in the total volume of MAs (MAV) was evident in the liver and spleen. Mean hepatic MAV (range in seasonal means, C: 6.4-23.1 mm³; S: 15.7-48.7 mm³) and mean splenic MAV (C: 7.3-12.6 mm³; S: 16.0-33.0 mm³) differed significantly among seasons and were significantly greater in females and in Severn River fish. Age and river were the most influential factors, suggesting that increased MAV in Severn River fish resulted from chronic exposures to higher concentrations of environmental contaminants. Hepatic MAV was directly related to the relative volume of copper granules in the liver. Less influential factors on splenic MAV included fish condition, trematode infections, and granulomas, indicating possible functional differences in MAs by organ. While organ volumes were strongly linked to gonadosomatic index (GSI) and reproductive phase, the reason for seasonal differences in MAV was less clear. Water temperature, salinity, and dissolved oxygen were not significantly related to MAV, and indicators of reproductive phase (hepatosomatic index and GSI) were significant but less important in explaining variation in MAV.