Aquatic nontarget organisms are exposed to fluctuating concentrations or sequential pulses of contaminants, so we need to predict effects resulting from such patterns of exposure. We present a process-based model, the Threshold Damage Model (TDM), that links exposure with effects and demonstrate how to simulate the survival of the aquatic invertebrate Gammarus pulex. Based on survival experiments of up to 28 days duration with three patterns of repeated exposure pulses and fluctuating concentrations of two pesticides with contrasting modes of action (pentachlorophenol and chlorpyrifos) we evaluate the new model and compare it to two approaches based on time-weighted averages. Two models, the Threshold Damage Model and the time-weighted averages fitted to pulses, are able to simulate the observed survival (mean errors 15% or less, r2 between 0.77 and 0.96). The models are discussed with respect to their theoretical base, data needs, and potential for extrapolation to different scenarios. The Threshold Damage Model is particularly useful because its parameters can be used to calculate recovery times, toxicokinetics are separated from toxicodynamics, and parameter values reflect the mode of action.