The minus end-directed microtubule motor cytoplasmic dynein is responsible for the intracellular movements of many organelles, including nuclei and endosomes. The dynein heavy chain contains a C-terminal motor domain and an N-terminal tail domain. The tail binds other dynein subunits and the cargo-interacting dynactin complex but is dispensable for movement of single dynein molecules in vitro. Here, we identified a mutation in the Aspergillus nidulans heavy chain tail domain, nudA(F208V), which causes obvious defects in dynein-mediated nuclear positioning and early endosome movement. Astonishingly, the nudA(F208I) mutation in the same position does not cause the same defects, suggesting that a subtle difference in the size of the amino acid side chain at this position has a significant consequence. Importantly, our biochemical analyses indicate that the nudA(F208V) mutation does not affect dynein subunit interactions and the mutant dynein is also able to bind dynactin and another dynein regulator, NUDF/LIS1. The mutant dynein is able to physically interact with the early endosome cargo, but dynein-mediated early endosome movement away from the hyphal tip occurs at a significantly reduced frequency. Within the small group of early endosomes that move away from the hyphal tip in the mutant, the average speed of movement is lower than that in the wild type. Given the dispensability of the dynein tail in dynein motility in vitro, our results support the notion that the structural integrity of the dynein tail is critical in vivo for the coordination of dynein force production and movement when the motor is heavily loaded.