This report details activities associated with the biannual Regional Monitoring Program for Water Quality in the San Francisco Estuary (RMP) water cruise. The RMP water sampling program was redesigned in 2002 to adopt a randomized sampling design at thirty-one sites in place of the twenty-six “spine of the Estuary” stations sampled previously. In 2007, the number of sites was decreased to twenty-two stations, combined probabilistic and historic, and it remains as such for 2021.