Aquatic risk assessment can be improved if we are able to quantitatively predict the effects resulting from sequential pulsed exposure to multiple compounds. We evaluate two modeling approaches, both extended to suit multiple compounds, the semi-mechanistic threshold damage model (TDM), and a model based on time-weighted averages (TWA). The TDM predicts that recovery of damage to Gammarus pulex from exposure to chlorpyrifos takes longer than that from exposure to carbaryl and consequently that the sequence of exposure matters. We measured survival of the freshwater invertebrate Gammarus pulex after sequential pulsed exposure to carbaryl and chlorpyrifos. Two groups of organisms were exposed to a first pulse of either carbaryl or chlorpyrifos for 1 day and then, after a recovery period of two weeks, to a second pulse with the other compound. The comparison of mortalities caused by each pulse, as well as combined mortalities in both treatments, show that the sequence of exposure to pulses of contaminants does indeed matter. Previous exposure to chlorpyrifos leads to significantly increased mortality from subsequent pulses of carbaryl, but not the other way round. The TDM facilitates a process-based ecotoxicological explanation by simulating the recovery dynamics and outperforms the TWA model.