The ability to assess the activity of gonadotropin-releasing hormone (GnRH) neurons has been greatly enhanced by transgenic animal models with targeted expression of green fluorescent protein (GFP). It has yet to be demonstrated however, that the GnRH system continues to exhibit a full range of normal physiologic functions in the presence of such genetic manipulation. Accordingly, we have used repetitive blood sampling via indwelling venous catheters to define LH secretory patterns in normal and transgenic mice. Transgenic females proved to be reproductively competent as defined by fecundity, appropriate cyclic changes in vaginal cytology in intact adult females, spontaneous LH surges as well as surges in response to steroid or mating stimuli. The expression of c-fos following such steroid treatment and mating in ovariectomized transgenics was similar to the expression previously reported in nontransgenic mice. Likewise, the percent of retrogradely labeled GnRH neurons was similar to that reported in non-transgenic mice. However, episodic LH secretion, an index of GnRH pulse-generator activity, was dramatically compromised in ovariectomized female transgenics as compared C57BL6 controls of both sexes and castrated transgenic males. Taken together, these findings suggest that the GnRH pulse generator is selectively impaired in ovariectomized females in which GnRH neurons express GFP.