Blue crabs affected with shell disease displayed a wide array of pathologies in response to this very common affliction. Grossly, shell disease lesions most commonly presented as variably sized brown to black foci. Such lesions ranged from very small (1 mm2) to locally extensive (up to 200 mm2 in area). The larger of the melanized lesions sometimes appeared ulcerated. The most severe lesions observed (Pamlico River shell disease-PRSD) resulted in loss of up to 25% of the entire carapace. A diverse bacterial flora consisting of aeromonads, vibrios and five other genera were isolated as the predominant organisms from shell disease lesions. Fungi were rarely observed in larger lesions. Protozoa and algae were also rarely observed on the surface of some lesions. Histologically, lesions ranged from mild erosion of the epicuticle and outermost layers of the calcified endocuticle to more extensive endocuticle erosion with accompanying inflammation. In the most severe cases, there was total loss of the endocuticle and epidermis, with pseudomembrane formation, intense haemocyte infiltration, and involvement of adjacent viscera. There was no apparent relationship between the size of gross lesions and their histological severity (as defined by the extent of tissue damage), suggesting that gross examination of shell disease lesions is not a reliable method for assessing the damage to affected blue crabs.