Differential pathogenesis was observed in two species of fish naturally infected with the pentastome Sebekia mississippiensis. Mosquitofish (Gambusia affinis) showed a mild inflammatory response to developing nymphs, whereas swordtails (Xiphophorus helleri) had an extensive granulomatous inflammatory reaction with accompanying hemorrhage, myositis, and myodegeneration. This suggested that certain species of tropical fish reared in the southeastern United States may be at risk to potentially harmful infections with this parasite.