Workers of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), range in size from ≈0.5 to 1.5 mm in headwidth. Such size variation is thought to enable a more efficient division of labor, because some worker sizes may be better suited to performing particular tasks. Here, I focus on the task of nest defense, where efficiency and effectiveness may depend on having appropriately sized workers respond to particular types of threats. Specifically, I tested whether the size of responding workers differs between two magnitudes of nest disturbance (light, insect-like versus heavy, vertebrate-like), and I investigated how both sting length and the amount of venom workers contain, key defensive traits, vary with worker size. Workers responding to heavy, vertebrate-like nest disturbances were larger than those responding to light, insect-like disturbances. Between the light and heavy disturbances, the proportion of minor (small) workers responding dropped, whereas that of major (large) workers increased five-fold. Although the relationship between sting length and worker size is not directly proportional, the average sting length of majors is ≈0.20 mm (or 40%) greater than that of minors, with little overlap in range. The relationship between worker size and the amount of venom they contain is also positive. So, vertebrate-magnitude nest disturbances are met with greater proportions of large S. invicta workers than are insect-magnitude disturbances, and these larger workers bring with them longer stings and larger venom arsenals, which may increase their effectiveness against such relatively large, thicker-skinned threats.