The spontaneously diabetic BB Wistar rat shows many characteristics analogous to human insulin-dependent diabetes (IDDM). These include inappropriately normal immunoreactive glucagon in the presence of hyperglycemia, absolute hyperglucagonemia with severe ketosis, and hyperresponsiveness to exogenous arginine in vivo. We used an in situ pancreas preparation to further study portal vein glucagon responses to intravenous arginine. In normal rats, magnitude of response was correlated with prestimulation levels. Basal levels were significantly increased in hyperglycemic diabetics compared to controls, but responses to arginine were attenuated in both absolute and relative terms. Comparisons of responses with poor and good prior diabetes control showed no significant differences. Thus, a further anomaly of glucagon secretion has been identified in these rats.