The antibody responses of spontaneously diabetic Chinese hamsters to sheep erythrocytes was investigated. After primary challenge, total antibody production of the diabetics was only 50% or less than that of nondiabetic controls, and little or no switchover to IgG production occurred. After second challenge, total antibody of diabetics was still reduced compared with controls. Some switchover to IgG did occur after second challenge but was only 40% that of controls. Poor antibody response was not related to abnormal glucose metabolism since low titers and lack of IgG was found in euglycemic prediabetics. Additionally, genetic nondiabetics rendered hyperglycemic by streptozotocin responded normally, similar to euglycemic controls. The impaired humoral antibody response of the diabetic hamster is similar to that reported for some human diabetics and makes this animal model attractive for studying the consequences and possible causes of diabetes-dependent impairment of immune responses.