The mechanism of cumulus oophorus formation with the follicular growth has been little observed. In order to make clear about it, the possible existence of a granulosa cell growth factor (GGF) in the oocyte was investigated by using the Mitotic Index (MI) (%0) of granulosa cells (GC) in human antral follicles. In each follicle, GC were divided into two groups, cumulus and mural GC, on the basis of the distance from the oocyte. The MI of cumulus GC was 8.2 +/- 0.5 (M +/- SE), constantly high in value with no relation to the follicular diameter, and two fold higher than that of mural GC, 4.7 +/- 0.4 (p less than 0.001). In general, Estradiol (E2) is well known as a granulosa cell growth factor. Hence, we investigated whether oocyte had E2 to know how E2 participates in the cumulus oophorus formation, by using the enzyme histochemical study. E2 content of the oocytes measured by Multi-Micro-Spectrophotometer in preantral and small antral follicles in which GC actively proliferate were 13.6 +/- 0.8% and 10.2 +/- 0.7% respectively, and higher than that of in large antral follicle, 7.6 +/- 1.0%. To examine the origin of E2 in oocytes, oocytes, GC and follicular fluid were measured using porcine ovaries. E2/protein of oocytes was 34.1 +/- 6.4 (pg/mg. prot) and that of GC was 10.2 +/- 2.8. It means that the origin of E2 may be from the oocyte itself. These results suggest, E2 in oocytes is estimated to be one of the oocyte factor to stimulate the granulosa cell proliferation and E2 plays a crucial role in the cumulus oophorus formation.