A lobster die-off significantly reduced the 1999 fall landings in western Long Island Sound. The die-off corresponded in time with the application of pesticides for the control of mosquitoes that carried West Nile virus, a new emerging disease in North America at the time. To determine the possible implication of pesticide application as a direct cause or contributing factor in the die-off, we studied the effects of experimental exposure to resmethrin on the health of lobsters. Lobsters (Homarus americanus) were exposed in 80-L tanks, and the direct toxicity as well as sublethal effects on the immune and endocrine system were determined. The 96-h LC₅₀ for resmethrin on single exposure was greater than 1 μg/L, the highest concentration tested in our experiments, whereas the 14-day LC₅₀ was 0.75 μg/L. Phagocytosis was significantly decreased 5 days after a single exposure to initial water concentrations of 1 and 0.1 μg/L, as well as after weekly exposure to 0.1 μg/L (week 3 and 4) and 0.01 μg/L (week 4). Cell counts varied widely and inconsistently upon exposure to resmethrin. Evaluation of phagocytosis is a sensitive indicator of subtle sublethal effects of resmethrin. Crustacean hyperglycemic hormone (CHH), a potential stress-related hormone in lobsters, was measured in the hemolymph of the chronically-exposed animals. Significant increases in CHH concentrations were observed after 4 wk of exposure to 0.1 μg/L. Whereas it is yet unknown if the concentrations at which toxicity was documented were ever encountered by lobsters in Long Island Sound during the 1999 die off, exposure resulting in the modulation of their immunology and physiology could likely have contributed to increasing lobster susceptibility to infectious diseases.