The cumulative effects of urban pollution and the presence of toxic phytoplankton in bivalves are not well understood. The purpose of this study was to determine the impacts of urban and algal pollution on wild Mya arenaria clams in the St. Lawrence Estuary. Clams were collected during low tide at sites differing in urban population (S1: 100; S2: 675; S3: 2,500; and S4: 50,000 inhabitants) in areas susceptible to toxic algal blooms and analyzed for immunocompetence (hemocyte density, viability, phagocytosis and oxidative burst/oxygen reactive species), energy reserves (sugars and proteins) and neural activity (acetylcholinesterase). Total phytoplankton counts in surface waters at the four sites, in decreasing order, were S3>>S1>S4 and S2. However, toxic phytoplankton species counts at the four sites were different: S4>>S1>S2>S3. The most abundant toxic species was Pseudo-nitzschia delicatissima, which is responsible for amnesic shellfish poisoning. Multiple regression analysis showed that toxic phytoplankton counts were significantly correlated with urban population size (β = 0.89) and with total phytoplankton (β = -0.25), suggesting that large populations favored algal bloom proliferation. Factorial analysis showed that toxic phytoplankton counts and population size were closely associated with reactive oxygen species production in hemocytes and increased AChE activity in clams, which is consistent with the cholinergic properties of some toxic algae. Total phytoplankton loadings were associated with increased energy reserves and hemocyte density. The data suggest that urban pollution contributes to algal production and that the effects of both could combine in clams, especially in stimulating AChE activity and the production of ROS in hemocytes.