In fasting nondiabetic subjects, insulin is secreted in regular pulses every 12 to 15 minutes, but patients with non-insulin-dependent diabetes lack regular oscillatory insulin secretion. To investigate whether abnormal insulin oscillations are an early feature of diabetes, we studied 10 minimally glucose-intolerant first-degree relatives of patients with non-insulin-dependent diabetes and 10 controls matched for age and obesity. We performed a time-series analysis of fasting plasma insulin levels in blood samples obtained at 1-minute intervals for 150 minutes. Fasting plasma glucose levels were higher in the relatives than in the controls (mean +/- SD, 5.4 +/- 0.7 vs. 4.4 +/- 0.3 mmol per liter). Autocorrelation of pooled data showed no regular oscillatory activity in the relatives but a 13-minute cycle in the controls (r = 0.23, P less than 0.001). Similarly, Fourier transform analysis showed no significant peak in the relatives but the expected significant peak at 13 to 14 minutes in the controls (P less than 0.05). First-phase (0 to 10 minutes) insulin secretory responses to glucose administered intravenously were not significantly impaired in the relatives (geometric mean, 188 pmol per liter [26.2 mU per liter]; range of SD, +103 to -67 pmol per liter [+14.4 to -9.3 mU per liter]), as compared with the controls (geometric mean, 231 pmol per liter [32.2 mU per liter]; range of SD, +131 to -83 pmol per liter [+18.2 to -11.6 mU per liter]). We conclude that abnormal oscillatory insulin secretion may be an early phenomenon in the development of non-insulin-dependent diabetes.