Estradiol profoundly influences GnRH secretion during the follicular phase of the estrous cycle of the sheep. Estradiol not only regulates the frequency and amplitude of GnRH pulses, but also produces qualitative changes in its pattern of release and induces a sustained GnRH surge during which discrete pulses are not readily evident. In this study, we tested the hypothesis that qualitative changes in GnRH secretion are an integral part of an estradiol-induced change in the mode of operation of the GnRH neurosecretory system that leads to generation of the GnRH surge. This was achieved by the measurement of GnRH in samples of pituitary portal blood collected at 1-min intervals for an 11-h period encompassing the pre- and early surge periods in an artificial follicular phase model. In each of the seven ewes studied, a highly characteristic alteration in the moment to moment pattern of GnRH was observed. This consisted of a progressive change from a strictly episodic pattern of GnRH release to one containing both episodic and nonepisodic components and, after amplification of both components, a period of extremely high values during which individual episodic increases were no longer readily recognizable. Preliminary mathematical modeling of the data suggested that these patterns could be produced by a change in GnRH from a predominantly low to a mixture of low and high amplitude inputs. Similar changes in minute to minute patterns of GnRH secretion were observed during the natural follicular phase. These findings are consistent with the hypothesis that estradiol induces the GnRH surge by altering the mode of neurosecretion, rather than by merely causing quantitative changes in the episodic pattern of release.