Repeated injections of recombinant human (rh) activin-A over a 2- to 3-day period are reportedly needed to stimulate the in vivo secretion of FSH. In this paper we present results showing that acute treatment with rh-activin-A caused marked and dose-dependent increases in plasma FSH, but not LH, levels in adult female rats. After one injection, maximum FSH release was observed 4 h after the administration of activin, while two injections of 100 micrograms activin/kg, 5 h apart, maintained elevated FSH levels for more than 10 h in intact diestrous day 1 females. Removal of the GnRH drive by pretreatment of ovariectomized animals with the GnRH antagonist ([Ac-D2Nal1,DCpa2,D3Pal3,Arg5,D-p-methoxyphenyl) 5- oxo-2-amino-pentanoic acid6, DAla10]GnRH; 100 micrograms/kg;) or repeated injections of the GnRH agonist ([DTrp6,Pro9,NEt,NH2]GnRH; 1 microgram/h for 5 days) did not prevent the stimulatory action of activin. Concomitant treatment with rh-inhibin-A (30 micrograms/kg], on the other hand, completely blocked FSH secretion induced by 100 micrograms activin/kg. These results indicate that activin-A is a powerful stimulus for FSH secretion in the female rat and exerts this effect independently of GnRH.