Oscillatory secretion of endocrine hormones is a widely recognized phenomenon. In man, as well as other species (dog, monkey), during the basal state insulin secretion is oscillatory and, on average, regular with a 13-min periodicity. In NIDDM there is a loss of regular oscillatory activity, being shorter in duration and irregular in nature. First-degree relatives of NIDDM subjects with normoglycaemia and obese normal subjects also exhibit this change, reverting to the regular oscillatory characteristic following weight loss in the latter group. The regular insulin secretory oscillations seen in the fasting stage in normal subjects are completely lost by raising the basal glucose concentration only marginally to about 6 mmol l-1. Thus, regular oscillations reflect a 'contented' beta-cell. Also, in states of hyperglycaemia, pulsatile exogenous insulin is more effective than continuous administration. Additional studies indicate that it is the periodicity of the insulin secretory oscillations and the rate of rise of the first phase insulin secretion in response to a glucose challenge which are the main candidates for successful signalling. Irregular oscillations of insulin can be used as an early marker of beta-cell under stress, but not as a fixed phenotypic marker.