Use of pyrethroid pesticides, which are highly toxic to aquatic organisms, has increased substantially over the past decade. In 2006, the pyrethroid pesticides cyfluthrin and permethrin were measured in Sacramento-San Joaquin (SSJ) Delta (CA, USA) water at 5 and 24 ng/L (pptr), respectively. To elucidate any interactions between the two pyrethroids, a 10-d laboratory exposure was performed with 7- to 14-d-old amphipods (Hyalella azteca). Cyfluthrin and permethrin were tested singly and in combination at detected levels and also at half and twice the detected levels, both with and without the addition of 25 ppb of piperonyl butoxide (PBO). Mortality in all treatments was significantly higher than in controls, with the median lethal concentration (LC50) for permethrin with PBO (13.9 ng/L) and the LC50s with and without PBO for cyfluthrin (5.7 and 2.9 ng/L, respectively) at or below levels measured in SSJ Delta water samples. The LC50 for permethrin alone was estimated to be 48.9 ng/L. To evaluate combined toxicity, logistic regression models containing terms for concentrations of cyfluthrin, permethrin, and PBO, as well as models containing all possible combinations of these terms and interactions, were run and compared using Akaike's information criterion. The most parsimonious set of models indicated slight antagonism between cyfluthrin and permethrin. Results indicate that a dissolved mixture of cyfluthrin and permethrin is toxic at environmentally relevant concentrations in the water column.