Infection of pregnant or non-pregnant mice with Coxsackieviruses B1, B3, B4 or B5 produced a severe pancreatitis consisting of a degeneration of the acinar cells, loss of zymogen granules, infiltration of mononuclear and plasma cells and a replacement of the exocrine tissue with fatty tissue. Coxsackieviruses B2 and B6 did not cause these changes in the period up to 6 weeks following virus injection. Suckling mice did not appear to be more susceptible to pancreatic damage due to these two viruses. Sequential studies on the development of Coxsackievirus B-induced pancreatic lesions indicated that although the changes due to B1, B3, B4 or B5 were similar in type, B3 and B4 exhibited a more rapid action in the tissue and more severe lesions than either B1 or B5. In this work, none of the Coxsackie B viruses examined elicited pathological changes in the islets of Langerhans detectable with the light microscope.