Harmful algal blooms are now recognized as a significant threat to the Chesapeake Bay as they can severely compromise the economic viability of important recreational and commercial fisheries in the largest estuary of the United States. This study describes the development of empirical models for the potentially domoic acid-producing Pseudo-nitzschia species complex present in the Bay, developed from a 22-year time series of cell abundance and concurrent measurements of hydrographic and chemical properties. Using a logistic Generalized Linear Model (GLM) approach, model parameters and performance were compared over a range of Pseudo-nitzschia bloom thresholds relevant to toxin production by different species. Small-threshold blooms (???10cellsmL-1) are explained by time of year, location, and variability in surface values of phosphate, temperature, nitrate plus nitrite, and freshwater discharge. Medium- (100cellsmL-1) to large- threshold (1000cellsmL-1) blooms are further explained by salinity, silicic acid, dissolved organic carbon, and light attenuation (Secchi) depth. These predictors are similar to other models for Pseudo-nitzschia blooms on the west coast, suggesting commonalities across ecosystems. Hindcasts of bloom probabilities at a 19% bloom prediction point yield a Heidke Skill Score of -53%, a Probability of Detection ~75%, a False Alarm Ratio of ~52%, and a Probability of False Detection ~9%. The implication of possible future changes in Baywide nutrient stoichiometry on Pseudo-nitzschia blooms is discussed. ?? 2010 Elsevier B.V.