Disease outbreaks, skin lesions, fish kill events, and reproductive abnormalities have been observed in wild populations of bass in the Chesapeake Bay watershed. Occurrence of synthetic and natural hormones from wastewater treatment plants and livestock operations, pesticides from agricultural lands, and phytoestrogens from cover crops have been implicated as potential causes of these adverse effects. Late summer to fall is the period of early gonad recrudescence in adult bass when spermatogenesis and oogenesis begin for the upcoming spawning event in spring. Our objective was to assess whether early gonad recrudescence was a period of sensitivity for inducing immunomodulation. Adult largemouth bass (LMB; Micropterus salmoides) were exposed in outdoor pond mesocosms from post-spawning (July) through early gonad recrudescence (November) to either a model estrogen, 17alpha-ethinylestradiol (EE2; 2.4 ng/L), a mixture of endocrine-active substances commonly detected in the Chesapeake Bay watershed (MIX; 5.4 µg atrazine/L and 47.9 ng estrone/L), or a solvent control. Immune endpoints including mitogenesis and respiratory burst were assessed in fish sampled during December and April.