In many estuaries worldwide, climate trends together with human diversion of fresh water have dramatically impacted the benthos. Such impacts have sometimes been complicated by exotic species, whose invasion and persistence can be mediated by wide variations in freshwater inflow. Monitoring such changes usually involves periodic samples at a few sites; but sampling that does not recognize variation at a range of spatial and seasonal scales may not reveal important benthic trends. San Pablo Bay, in northern San Francisco Bay, has extreme fluctuations in freshwater inflow. This bay also experienced a major benthic change with introduction of the Asian clam (Potamocorbula amurensis) in 1986. This species initially displaced the former community, but later appeared to vary in abundance depending on site and freshwater inflow. To investigate such patterns and provide guidelines for research and monitoring, we took 1746 core samples at six sites around San Pablo Bay from 19 October to 17 December 1999 and from 6 March to 19 April 2000. Most biomass consisted of the clams P. amurensis,Macoma balthica and Mya arenaria. Potamocorbula amurensis dominated the benthos at most sites in the fall and recruited a new cohort during winter, while there was weak recruitment in M. balthica and none in M. arenaria. At most but not all sites, densities of P. amurensis and M. arenaria declined dramatically over winter while M. balthica declined only slightly. The dominant clams had patch diameters >5 m at most but not all sites, and some showed inconsistent patch structure at scales of 100–1400 m. In this semiarid estuary with highly variable freshwater inflow, samples for research and monitoring should include multiple sites and seasons, and samples within sites should be ≥5 m apart to account for between-patch variation. Species abundance in winter 1999–2000 appeared to be affected by high freshwater inflows in 1997–1999, while spatial patterns were probably most affected by post-settlement dispersal and mortality.